The topic today is a common, a very common quality assurance activity, which is the validation of analytical procedures and other associated activities like verification and transfer. Those things are represented in the USP in chapters 1225, 1224, and 1226. We will also talk about the new ideas for validation, which are now represented in a new proposed chapter in USP chapter 1220, which is now open for comments until the end of November. Let me start saying a few words about what is the importance of validation. And when you develop a product, I mean, the methods used to demonstrate any quality attribute in a product needs to be validated. And this is from through the development until that the product is in the market. The validation process will provide evidence that systems and methods are suitable for the intended use. And that phrase, suitable for the intended use, will be present in all the activities associated with validation. The Code of Fair Regulation in the US says that the accuracy sensitivity, specificity, and reproducibility of this method employed by the firm should be established and documented. That is the other important part of the validation, which means that all the experiments you will perform in order to demonstrate the suitability for the intended use will be documented. And finally, there should be evidence that the method that we have been validated at one time at the beginning maintain this state of validation through the life cycle, which means from the inception of the method through the retirement of the method. And this is something that is not well represented in the current validation scheme, but it is an important piece in the idea of the methods life cycle management. The definition of validation, as I was anticipating, is this one is the one that is in Chapter 225, Validation of Compendial Procedures. It says that the validation of an analytical procedure is the process by which it is established by laboratory studies that the performing characteristics of the procedure meet the requirement for the intended analytical application. A couple of important elements in this definition, first of all, is the demonstration is based on laboratory studies. So you have to perform certain number of experiments to demonstrate that the method is validated. And the more important and is underlined here is the idea that you have to demonstrate through the validation results that the method meet the requirement for the intended analytical application. You have to conclude that with the level of variability you determine in the method, this method can be used for the application you need. Currently in USP, we have four chapters more or less related to the validation of analytical procedures. Those are Chapter 225, Validation of Compendial Procedures. This is the first chapter that was introduced in USP on this topic a long time ago. The idea is to reproduce more or less the text in ICHQ2. So it's more focused in chromatographic procedures. However, you can adapt the validation protocol in 225 to different types of methods, not all, but some of them. Then we introduce another chapter 226, Verification of Compendial Procedures. This is to demonstrate, it's a guidance on how to demonstrate the suitability at the time of the implementation in the lab. And we first specifically, at least from our perspective, two pharmacopoeial procedures. We introduced 224, Transfer of Analytical Procedures. This chapter focused on the transfer between laboratories. We usually say that if the method is in the pharmacopoeia, the appropriate activity will be the verification of the transfer. However, a mix of activities associated with verification of transfer can be done in any case. The latest member of the family is chapter 1210, Statistical Tool for Procedure Validation. This is a chapter that has intention to provide some statistical guidance on how to demonstrate a more important performance characteristics of the method, namely accuracy, precision, and limit of quantitation. The performance characteristics are those defined in the ICAQ-2 and in 225, and we will not go into the details of this, but you know that the accuracy is to demonstrate if the real, the reportable result deviates from the real result. Precision is the dispersion of the results around the mean, and it's defined in three levels. Repetibility and reproducibility, usually pharmacopoeia focus in the first two, repetibility and intermediate precision, because reproducibility data is not always a by-level. However, as the method are published in a pre-official state, like in Europe, pharmacopoeial following the U.S., Japanese pharmacopoeial following Japan, that gives the user, the stakeholders, the opportunity to reproduce the method as is written in the, as is being proposed in the pharmacopoeia, and provide data to the pharmacopoeias in terms of any problem you will face, you face when you try to reproduce the method. It's a sour way to obtain something close to the reproducibility data. Then we have specificity, probably more important, which is to demonstrate that the analyte is being quantified without interference. Limit of detection and limit of quantitation, this is for trace elements, trace components in a matrix. You have to demonstrate that you are able to detect and quantify the analyte at the appropriate level. Linearity, sometimes the definition is conflictive, because in ICH it's unclear, but we will define here linearity as the response function between the analyte and the instrument response. This is what you do when you do the graph between having the concentration in one axis and the response of the detector or wherever you're using to measure in the other one. Not always is linear. Range is the lower and higher concentration where the method will be used. And finally, robustness, another sometimes conflictive parameter, because we can see the robustness not part of the validation protocol, but part of the method development. So in robustness, you define tune of the method that has been developed. This is where you will identify the system suitability parameters, et cetera. This table is in ICAQ2, very similar, and in 12.25. And I think it's the basis of the current concept of validation and even verification and transfer probably too. And it's defining what kind of experiments you have to do, depending the type of method you're trying to validate. And the methods are divided in four categories. Category one is when you're measuring the main component in a matrix. Category two can be quantitative or limit test. This is for impurities, so a small component, which is in a low concentration in the matrix. Category three is for performance testing. This is unique in USB. It's not in ICAQ2. And finally, category four, which is for identification methods. So if you see this, you follow this table, you will have a nice, define a nice protocol for validating your method. However, it's very difficult to base, after doing all this experiment, to demonstrate that the method is really suitable for the intended use. And that is the focus of the new ideas on validation, which is the one the topic I will talk about at the end of the presentation. Pharmacopias, USB also allows the use of alternative methods to the methods included in the Pharmacopias. The requirement of using an alternative method, according to USB, this is in the general notices, topic 630, is that the method needs to be fully validated. Your alternative method needs to be fully validated and must produce comparable results to the compendial method or procedure with an allowable limits established on a case-by-case basis. So in order to demonstrate, I would say, the equivalency, we're trying to not to use the word equivalency anymore. We are talking about comparable results. It's by using a type of a two-anxiety test, a statistical test to determine the comparability. And in order to do that, you have to pre-establish a range of the results where the method will be considered equivalent. For more details on this approach, I will recommend for you to look into Chapter 1010 in USB, which provides examples on how to demonstrate equivalency or comparability using the two-anxiety test. So what about verification? So we identify what is validation. You will do validation when the method is new and developed by you. And also when you use a pharmacopoeial procedure with sufficient level of modification that requires full validation. Now, in cases where you will take the method as it's written in USB and will try to implement in your lab, the first thing you have to do is to verify the method. And the need for verification is not a USB requirement, it's in the color fair regulation. And this text, which is reproduced also in Chapter 1225, Validation of Companial Procedure says that users of analytical methods described in the USB and F have not required to validate accuracy and reliability of these methods, but merely verify their suitability and their actual conditions of use. Which means that at the time of use the method in your lab, you have to do some kind of a, some people call minivalidation, we call verification, to demonstrate that the analytical operations, including the matrix, instrument, or analyst are appropriate for the use of the method. Another definition is included in Chapter 1226, Validation of Companial Procedures. And it says that verification consists of assessing selected analytical performance characteristics, such as those that are describing Chapter 1225, to generate the appropriate relevant data rather than repeating the validation process. So it's not going into the details, but the concept is there are certain things in the list of performance characteristics that are critical in order to demonstrate that the method as is being used in your lab is suitable. And part of the difficulty of interpreting Chapter 1226 is the fact that people sometimes don't understand that the decision of what are the more critical parameters lies on the shoulders of the user. So the user needs to use their scientific knowledge to determine what is the appropriate experiment to demonstrate that the method is verified. And we will discuss some of the approaches you can follow in order to identify those characteristics. So if we try to compare the two activities, the validation and the verification, you will realize that when you do validation, you are trying to challenge a method, the procedure. And for doing that, you use a well-defined sample. Usually when you do validation, the composition of your sample is well-defined. Sometimes you use a reference material for doing the validation. Also, you assume that your analyst is well-trained because you are not trying to identify differences caused by the analyst. You are trying to determine or identify variability caused by the method. And also, you assume that the method is well-calibrated. So again, in validation, your focus is the analytical method. When you do verification, what you are trying to do is challenges the analytical operations associated with the repetition of the method, also the analytical matrix. And you will use a well-defined method, which is the pharmacopeal procedure. So when we do verification, our focus is not now the method, but the analytical laboratory, including the analyst instrument and the sample matrix, the matrix of your product. So if we put all those together, you will see that from an analyst's perspective, if you are working in a GMP environment, you can assume that the analyst has the appropriate education training and experience, as it is defined or required by the current GMPs. The same way, instrument needs to be calibrated, and that is also a GMP requirement. So we can still have those assumptions. The reagents used in the method usually are defined, well-defined with quality attributes in the pharmacopeas. So you know which is the appropriate reagent to be used in that particular method. So what is the main source of variability during the verification is the matrix, because the matrix contained in your product contains your XCPNs and all the components in the formulation, and those components may not be the same that were used when the pharmacopeal monograph was developed. So it is important to have this step when you define that your product, your matrix, is appropriate for the method that is written in the pharmacopea. Again, there is not such a generic protocol for verification, it is something that should be defined case by case more or less. But we can have some basic rules or some basic approach on what to do. And we know that specificity, for the reasons we explained before, is very important in the verification to demonstrate that any of the components in the matrix interfere with the quantitation of the analyte. This is very important. And obviously, in some cases, you know the matrix, you can identify, you can prepare a placebo matrix. So you have several tools to verify the specificity of the method. You can also determine peak purity using the appropriate HVLC detector. Then we have a QSEM precision. These two are the main, together with specificity, the main performance characteristics that needs to be tested during the verification. We have to demonstrate that the analyte is properly recovered within the range of the specification. And also, you can determine that the repetibility is appropriate during the, within the range of specification. Well, LOD only in limit test, but LOD is also important when you run an impurity test. And the idea is to demonstrate that, and this is probably more legal, people use different approaches, but one approach may be, if I'm able to quantify the impurity at 50% of the maximum specification, I will be sure that when I am quantifying an impurity and add the specification, I am in the middle of the range, so a QSEM precision or appropriate, etc. And finally, you don't need usually, unless you change the concentration of the standard solution, which is not the case in general, you don't need to test linearity. Again, if we define linearity as the response function between the analyte and the response of the instrument, this is an intrinsic property of the molecule that don't need to be tested again during the verification. Range is not need to be tested, range is already defined in the paracupial specifications. And robustness usually is part of the verification, as I said before, is more a component of the mental development. Very important, but it is in the mental development part. So this is about verification. Transfer is defined in chapter 1224. The transfer of analytical procedure is a documented process that qualifies a laboratory, the receiving unit to use an analytical test procedure that originated in another laboratory, which is the transferring unit, thus ensuring that the receiving unit has the procedural knowledge and ability to perform the analytical procedure as intended. Here, the focus is not the method, it's not the sample, it's the lab. So during the transfer, your intention is to demonstrate that the receiving unit has the appropriate personnel to run the test and the laboratory service as are appropriate for running the test and the instruments also are appropriate. So transfer is not an activity that is really closely linked to a pharmacopoeial procedure, because again, if the procedure isn't a pharmacopoeia, probably the verification is the appropriate test. So it was included in the pharmacopoeia just with the purpose to process the loop between all the associated or related activities with the generation of analytical data. There are four approaches for transfer, comparative testing, covalidation, revalidation, and transfer waiver. Comparative testing is more common way to do the transfer and basically is to analyze the sample from the same batch in one lab and then the other lab and demonstrate that the results obtained are equivalent. Again, in order to see an exercise of demonstrating equivalency between two results, go to chapter 1010 and you have a couple of examples there. The covalidation is the process for which we validate the method at the same time in both laboratories. We follow the 1225 as a general protocol for the validation. And you will try to demonstrate that the method is suitable by analyzing the, that the method is transferred by analyzing the validation results in one lab compared with the other. Problem here is that sometimes you may see differences and it is difficult to identify if those differences are caused by the method, because the method is not fully validated yet or is the lab. For that reason, always the comparability test is the more appropriate. Revalidation is again similar, is repeating the validation experiment in the receiving lab. And again here you may see difference between the results and depending how, when the method was validated originally, those differences may cause by some kind of a shift on the method behavior or the lab. And finally transfer waiver. There are situations where you can waive the need of doing a transfer, a formal transfer, and those four options are also listed in chapter 1224. The new product composition is comparable to that of an existing product and is analyzed by procedures with which the receiving unit already has experience. The analytical procedure being transferred is described in the USPNF and it's unchanged, so we will do verification there. But again, nothing prevents to use any combination of activities really, activities associated with the verification or the transfer. The analytical procedure transfer is the same or very similar to a procedure already in use or the personnel in charge of the development validation or routine analysis is being moved to the receiving unit. In those situations, the method don't need to be transferred formally. 1210 is a chapter that I presented at the beginning of the presentation. Again, is the latest member of the family in describe certain statistical approaches that can be used during the validation, focus in accuracy precision and the detection limit, and not the rest of the performance characteristics. Not all of them are described. One interesting point here is that the accuracy and precision are described in 1210 as one performance characteristic. So you can combine the accuracy and precision in one component, we can call total error, and 1210 explain how to do that. That is very important for the analytical lifecycle management because that is the approach we follow in that enhanced approach. Briefly, again, how we will define when to use validation and verification. When the method we are trying to implement is not validated, we will validate using 1225. If it's validated and it's compendial method, we will use verification 1226. If it's validated but it's not a compendial method, the appropriate activity will be transferred. And this briefly describe what are the different options for transfer depending on the situation. So if you're trying to transfer a method that is validated and cannot be weighed, you can use comparative testing. If not, you will try the revalidation. And on the other side, if the method is not validated, you can do a covalidation between the two methods. So I'm here, we describe or we discuss the traditional approach for validation verification and transfer. So what are the new ideas regarding validation? And I will start mentioning this document that FDA published in 2004 where the indications of the weakness of the actual validation process are mentioned. The document says that variability and or uncertainty in the measurement system can pose significant challenge when outdoor specification resource are observed. Measurement system variability can be a significant part of the total variability. Similar and repeating out of specification observation for different product across the industry and a less than optimal understanding of variability. Continuous improvement is difficult if not impossible in this situation. So the document acknowledged that the out of specifications not always are caused by deviations in the product. It also can be caused because the variability of the method had not be perfectly defined or qualified during the validation. In this way, this way, coverly method validation and transfer have become an exercise more focused on satisfying regulatory documentation requirements rather than understanding and controlling source of variability. Analytical procedures were validated at the beginning of the method lifecycle with little consideration of how well the method will perform in real work operation conditions. ICHQ2 often apply in the laboratory in a checkbox manner without linking the validation parameters to the fitness for purpose of the procedure. This is the key topics here. First of all, we know that we have to validate because is a regulatory requirement, but we are usually following ICHQ2. We will not link the method variability with the fitness for purpose of the method. And the second is that when we value the method once in lifetime and then the method is used with a little consideration about how the method will shift through the lifecycle. So those are the things that we are trying to address when we talk about validation and verification, sorry, when we talk about the lifecycle, analytical procedure lifecycle management. The first attempt to go into this direction in USP was the creation of the Validation and Verification Expert Panel in 2013. This group produced four documents which are those listed here in the pharma copial form so you can access them if you want to read because they represent the basis of the future development of Chapter 1220. The procedure lifecycle can be reproduced using this scheme. We will briefly discuss all these stages, but here what is important to notice is that there is a previous and initial activity which is to demonstrate or to identify what is the analytical target profile. This is a statement, a very simple statement that we identify what is the definition of CWT for the intended use, but from the perspective of the performance characteristics of the method. One that is defined will choose the technology, we will go into stage one which is procedure design, we will go into stage two which is procedure performance qualification and finally stage three, continue procedure performance verification. On all this process we will collect information and we will have to establish a knowledge management system to collect and archive all the necessary information regarding the whole story of the method. So what is the ATP, the first step in the process? The ATP is a prospective description of the desired performance for an analytical procedure that is used to measure the quality attribute. So we plan a method we need for measuring certain particular quality attributes of the product. We will define based on the specifications, based on the therapeutic window of the product it said that we will define what is the quality, the necessary quality of the reportable value we need and based on that we will create the ATP. When we create the ATP we will define what is the more appropriate technology for measuring that particular attribute. The ATP usually include the definition of the analyte, so what is the analyte, what are the components present in the matrix, what is the concentration range for the method where the method will be used and the accuracy and precision which will be acceptable for the reportable value. There are two examples in the chapter in the proposal of chapter 20. The first one is more or less based on the traditional approach of presented accuracy and precision as two separated parameters. The second one is more focused in the total error and it says that the distribution of total analytical error of the reportable value falls within the total analytical error range of plus minus certain percentage. It can be done using uncertainty, measurement uncertainty, etc. Any way to provide the minimum requirement for the quality of the analytical data will be appropriate. The stage one of the procedure is the method of design. Here we will define what are the methods parameters that allow compliance with the ATP criteria, so in other ways minimize the bias and provide the adequate precision. We will understand what are the effects of the procedure parameters on the performance, on the procedure performance, mainly usually known as robustness. We will optimize those performance characteristics including accuracy, precision, calibration model, selectivity, sensitivity. Finally, we will have a preliminary replication strategy for samples and standards, something that is not usually included in the traditional approach for validation or better development. And also, we will define the analytical control strategy, which implies the system suitability parameter and other tests that will assure adequate performance. The stage two is the qualification of the method. Here is where we actually do the actual validation. This is mostly focused in accuracy and precision. At this stage, if we are able to demonstrate that the accuracy and precision of the method is adequate within the range of the method, we can say that, and meet the ATP requirements, we can say that the method is qualified. Also, we have data generated during the stage one that includes the rest on the other performance characteristics like linearity and limit of quantitation, etc. So, at the end of the stage two, the replication strategy is confirmed, and it's confirmed that the performer of the procedure meets the ATP and other criteria. So, we are ready to implement the method. When the method is implemented, we go into stage three, which is the continued performance verification. So, the method may be transfer, may be used in the same lab. We will use it under different situations. However, we have a set of tests, which is more than the system suitability test that will help us to identify if the method is still performing within the ranges that was expected to be performed. So, the ATP criteria is still being met, and we will do that through the rest of the lifecycle of the method until the method is retired. So, just to finalize, the USB chapter validation verification on transfer will continue being the compendial guidance for these activities. So, you should not expect in the short term any big change in the way the pharmacopeia describe a validation verification transfer in these three chapters. Chapter 20, which is the one that is now in the PF, will provide directions for implementing an enhanced approach that encompasses analytical QVD and respect principles. So, the analytical lifecycle management incorporate, among other things, the idea of creating or using analytical QVD tools for the method development, and also is a risk-based approach, because the ATP is defined, the requirement for the reportable value, reportable result, is defined based on the risk we can accept for obtaining the reportable result. How this new approach may impact on existing mono and future monographs is being discussed. There are several points that needs to be discussed. For example, if there is a replication strategy associated with a particular ATP, probably that replication strategy should be incorporated into the method description in the monograph, which is a big departure from the current philosophy in the pharmacopeias, which describe only one standard one sample. Other aspects that have to be considered is based on the knowledge collected during the method development, it is possible to incorporate in the monograph the ATP, which is defining the quality of the reportable value, but also what are the appropriate adjustments that can be done in the method and the method still behave as expected. Something that we do actually in a genetic way, put in certain parameters, adjustment of certain parameters in Chapter 621, or in the chromatography chapter in the European Pharmacopeia. So those things are still discussed. Just an announcement, in December 8th, we are presenting together with the British Pharmacopeia, a workshop, Analytical Quality by Design, and the Method Analytical Life Cycle, one of the companional applications. In this workshop, we will discuss the activities in both pharmacopeias related to this topic, and also we will present examples. And I think that's all I have. This is my contact information. Also, if you are interested in other educational programs in USP, you have the link there. And also if you're interested in participating in USP activity as a volunteer, you also have the link there. Thank you for your attention. And let me know if you have any questions. Thank you. Thanks a lot Horatio for this wonderful presentation and very detailed presentation, even given the short time. We have indeed a couple of questions here. First question was, will the presentation be available? I think we can set it up as a PDF or ratio and provide to the participants, right? Yes, absolutely. Very well. Thank you very much. Okay. And now the more technical questions here, we will not be able probably to go through all questions today, but I have a couple of questions here that I think are interesting. The first question is, if method transfer between two companies was successfully concluded, the receiving labs still have to perform verification of methods? No, the transfer implies that the method is can be performed in the receiving lab with no further action. Excellent. Thank you. And another question is, even if there is no modification to the operating conditions or to the specifications, is there is there a kind of recommended frequency for revision of a validation study necessary? Well, yeah, that's a good question. And I have to say that usually pharmacopias are silent in terms of how often a quality assurance activity needs to be repeat. As if you go into the traditional approach for validation, the answer is yes, because methods are not static. They shift with the time. You use different reagents, different columns, different analysts, and the level of training may change. So it is recommendable to exercise the revalidation or at least some kind of reverification of the method. But obviously, USB or any other pharmacopia will tell you how often it needs to be done, because that depends on the use of the method and the characteristics of the lab. Thank you, Orishu. There's another question. Is the robustness parameter mandatory to prove for monograph methods? Usually, the robustness is not included in a verification protocol, because again, the verification has the purpose to identify where are the critical instrument parameters and how those critical parameters can be modified or adjust. And usually, that will not change. So it may be cases where it's needed. I cannot omission a situation where you need to reproduce the robustness. Now, you can see how the previous question and this question will disappear when we embrace the new idea of validation, because obviously, because you will do a continued verification of the method, you need to worry about revalidation. You are continuously monitoring the method. And regarding robustness, when you develop the method using the analyzer procedure, lifecycle management, you have enough data to identify all the robustness parameters and you will define, if you use HVD elements, you will define what is called the MODR, the method operable design region, which will indicate where the method can operate. Thank you. Another question we have here going in the same direction, I think, when the method is pharmacopayered and is used over years without any manipulation, is verification data still required? That's another good question. And I have to say that there is probably a glitch in the USB text, because when the chapter 1226 was incorporated, we included a clause, a grandfathering clause that says that methods that are already implemented at the time of implementation of the official stage of this chapter don't need to be re-verified. So you can use historical data to demonstrate that the methods have been verified. But after that, the expectation is that any new method after the implementation of 1226 needs to be verified. The problem is we will still leave that grandfathering clause in the chapter, so it's very unclear. But the idea is that everything that is coming to the lab now needs to be verified. Thank you very much. There's one question here going into our bioanalytical fields, and the question is the methods that are described in USB General Chapter 129, Analytical Procedures for Recombinant Therapeutic Monoclonal Antibodies. Do these methods need to be validated or verified as well? Well, I have to say that I'm not familiar with the content of the chapter, because it's in the bio department. It's not in the general chapters department. But again, what I can say is that when a genetic method is described in a chapter, when that chapter is referenced in an individual monograph, we can say that that method was fully validated for that particular purpose, and there is no need for validation. It's just the verification is the only thing you need. However, if you are using a USB method described in a chapter for a product that is not described in the USB, the idea is that you have to demonstrate that the method is suitable for your product. So maybe a more extensive validation is needed. Now, the point in this case, and again, I will excuse myself because I'm not familiar with the content, is that there is a common aspect in the monoclonal antibodies that makes me believe that many of the components, many of the quality, many of the performance characteristics of the method described in the chapter don't need to be reproduced. For a more extensive answer on this, I will recommend to contact the people in charge of the document in our bio department, Christian. I think you can direct the question to the right people. Yeah, I can. Thank you very much. And don't worry Horatio, this is the only bio question for today. Everything else is going directly over validation and verification. There's one question about alternative methods. There is no statistic data available for pharmacopayal methods. Do I need to implement the pharmacopayal methods first to generate data for statistic comparison when I want to set alternative methods? Yes. In order to, the way the use of alternative procedures is described in the general notices, and again, general notices is the document at the beginning of a USB that impact the whole, the whole pharmacopayal activities. The ways described imply that you have to generate some data using the method in the pharmacopoeia in order to accept or adopt an alternative procedure because you have to be certain level of comparison between the pharmacopoeial method and the alternative procedure. Thank you. There's one question that came up several times also for the example of excipients. So what if you have already verified a method on a certain material from one manufacturer, for example an excipient? Is it necessary to verify the test again on a similar material this time from another manufacturer? Okay. Well, very good questions, all very good questions. And there is some kind of a balance here because you may say, okay, I validate this method. This method is, I was able to identify the appropriate purity of my excipient and I can use the method. Now I changed the supplier of the excipient and now the composition of the excipient may be different. And at least, I don't know, a specificity probably needs to be tested again to be sure that any new component or impurity appears in the matrix that was not detected before. Now having said that, I have to say that if you have an appropriate process to qualify your suppliers, this step will not be needed because you have a previous contract with your supplier in terms of what is the expected quality of that particular excipient. So depending on the case, you may need to do it or you may not need to do it. I would say that for basic Euro compound type of excipient, the answer is you don't need it. I'm talking in the cases where composition of the excipient is more complex. Thank you. There is one question about harmonization or maybe harmonization at some point in time because the questioner is saying there's a new chapter published in Pharm Europa. So in the Pharmacopale Forum equivalent from European Pharmacopale, there's a published new chapter in Pharm Europa concerning a two-step process for the verification of Pharmacopale procedures. The chapter is 526, it's saying. In chapter 1226, so in our chapter, there is no clear distinction of these two steps. Is USP considering the review of this general chapter to harmonize with what Pharm Europa is saying or suggesting? Any of these chapters, verification, validation and transfer are in the PDG program. So there's no formal intention to harmonize these chapters. We started last two months ago, we started a new cycle with new committees and new experts in our committees. And now we are starting reviewing all our chapters. Validation, verification and transfer are now in the review of a new expert committee which is called Measurement and Data Quality and they are also owning chapter 1220. So I cannot assure that in the near future or in the future maybe some modifications in 1224, but so far there are no plans. Thanks a lot, Horatio. Another question is we have still five minutes and a few questions we can still take. So another question is why precision is only focused on repeatability and not on intermediate precision as well? I would say the contrary. Precision needs to be focused in intermediate precision because intermediate precision is where you have a more closed reproduction on how the method is used in the routine. So I would say I agree that precision needs to be focused in intermediate precision rather than in precision, which is a limited amount of data you collect. Yes, exactly. There's one question to your slide number 10. Do we always have to obtain positive limit of detection and limit of quantitation results at the level of 50% of the specification when verifying the method? No, and thank you for the question because I think I forgot to mention that that particular slide by no means is any list of requirements. This is a collection of things that we hear with the time that people are doing. It's not necessary to go that level at 50%. People who do that is because of the fact that because you don't know the distribution of the error around that result because you are in a low concentration, in order to be sure the appropriate amount of data are included within or outside the range, it's a good idea to verify the limit of quantitation in a lower level than the specification. So when you are in the specification, I would say the whole Gauss distribution of error is inside or outside the limit. But by no means that is a requirement or a mandatory activity. You can choose your verification protocol and acceptance criteria based on your knowledge of the product and the method. Thank you. One more question here. If the API manufacturer already has verified, validated the analytical methods used to determine related impurities in the API, is the finished product manufacturer then also required to revalidate, re-verify the method? Well, that is probably more a company decision. I will assume that this is a method that is not in the pharmacopoeia. It's a method that was developed and validated by the API manufacturer. Obviously, you will collect that information when you decided to buy that particular API in terms of what are the appropriate impurity profile, et cetera, and you will use that method. In terms of you want to revalidate that method, accept the validation protocol of the supplier or verify the method. I think it's more or less a company decision. At the end of the day, I'm not sure if it's the same everywhere, but at the end of the day, the responsibility of the purity of the particular compound is the pharmaceutical manufacturer. So you may choose what is the level of risk you want to have. Maybe we have two more quick questions possible. If the alternative method that we are using is a EP or JP compendial method, we have to perform a full validation or is it just a verification? That's probably a question for regulators. Is it a regulator who needs to accept or not the method coming from other pharmacopoeias? It's not a USP rule. Thank you, Horatio. And maybe the last question, please, can you repeat the difference between transfer and verification? Verification is not the ability of the lab to perform the analysis, right? Verification is where we will challenge all the analytical operations in the lab with this pharmacopoeial procedure, but using our sample. So it's the analysis, the instrument, the laboratory services, vacuum, water, air, et cetera, and the matrix. So we will focus on mostly in the matrix because it's the main source of viability, however, we assume that the instrument is well calibrated, the people are well trained, et cetera, et cetera. When you do transfer, you cannot have all those assumptions. What you are trying is to demonstrate that the laboratory operations, the instrument, the the analysis, et cetera, are appropriate for the method. So in one case, we focus in the matrix. In the other case, we focus in the lab. Thank you once more. Thank you very much, Horatio, for answering all these questions. There are many, many more. We cannot answer them today anymore. We will receive tomorrow probably the PDF of Horatio's presentation. There is his email address and please feel free to send him any question that you think has not been answered here during this webinar. So once again, thank you very much, Horatio, for the time and sharing your knowledge and experience here with us. And thank you also once more to the participants for spending this hour today with us on the validation transfer and verification of analytical methods. We have our next webinar in two weeks about dissolution and performance verification testing on dissolution. So thank you, Christian. Thank you very much, Horatio. And thank you for your attention. Thank you, everybody, and have a good day further on. Thank you. Bye-bye. Thank you. Bye.


I'm a mathematical biologist here at Harvard and before I begin my talk I would like to tell you what a mathematical biologist is and it's best explained with a short story. So there's a shepherd and a flock of sheep and the man comes by and says, if I guess the correct number of sheep in your flock, can I have one? And the shepherd says, OK, try. So the man looks and says, 83. And the shepherd is completely amazed because it's the right number. So the man picks up a sheep and wants to walk away. The shepherd says, hang on, if I guess your profession, can I have my sheep back? OK, try. You must be a mathematical biologist. How did you know?  So in my field it's important to get the numbers right. And today I'm talking about the evolution of cooperation, which is a very big topic because Darwinian evolution is based on natural selection and natural selection is a struggle for competition. And in such a struggle the question would be, why would we ever help anybody else? Why should I reduce my own fitness, so to say, to increase the fitness of somebody else? And that's the problem of evolution of cooperation. So in the atomic interaction here we have two people say, or two cells, you know, but let's talk about people here. And one is a donor and the other one is a recipient. The donor pays a cost and the recipient gets a benefit. And cost and benefit are measured in reproductive success and reproduction can be genetic or cultural. So we use the same framework to describe, say, people learning how to behave without genetic reproduction. We talk about cultural evolution then. So if you have this framework and if both people have to make a choice simultaneously between cooperation and defection, we get a very famous game. It's a game in the sense of game theory, a field of mathematics that was invented by Jonathan Neumann. And so what you see here is that my choice and your choice and then what is written in red is what you would get if these were the outcomes. So you have to look at this payoff matrix and now you have to decide for an action either to cooperate or to defect. And I will also decide between cooperation and defection so we will play the game simultaneously. So please look at the matrix and make a choice. Who wants to cooperate with me? Raise your hand. Who wants to defect? Very few defectors so many people haven't actually decided so I should say this is not an optional game in game theory. We also have optional games where there's a third column which means do nothing but this is not a prisoner's dilemma so you have to make a choice essentially. So this is how you should think about it. You don't know what I will do, let's assume I cooperate. If I cooperate you have a choice between B-C and B. So B is greater than B-C because B greater than C greater than zero so if I cooperate you want to defect. If I defect you have a choice between minus C and zero. So zero is greater than minus C so if I defect you also want to defect. Therefore no matter what I might be doing it is better for you to defect. And now if I analyze the game in the same way we both end up with defection, we both get zero points and then we are very disappointed because over there we would have had B-C points had we both cooperated. And that's precisely why it's called a dilemma. So the dilemma is that there's an incentive to defect but two cooperators are better than two defectors. For the group it is better to cooperate but for the individual there's always the temptation to defect. And that's the problem here and what I gave you is the so-called rational analysis that is offered by game theorists and economists to say that you cannot cooperate in the prisoner's dilemma as written here. But we have seen that people cooperate and this is also born out in experiments. So the question is why do people cooperate? I should say that as biologists we analyze the game slightly differently we don't need the concept of rationality. What I gave you was this rational analysis and a rational player is defined in the game theory sense as somebody who realizes what the Nash equilibrium is and plays the Nash equilibrium but most experiments show that people are not rational. So the interesting thing is biologists don't make use of that concept but come to the same conclusion. So if we have a mixed population of cooperators and defectors a defector always has a higher payoff than a cooperator. So therefore defection becomes more and more popular and this is how you make money. You make more and more money until everybody is a defector and the system breaks down. So here natural selection destroys cooperation, opposes what would be good for the population and leaves the population in a state of just defection. So therefore natural selection needs help to favor cooperation over defection. And this help is something that I summarize in five mechanisms. There has been work on this over the last 40 years and there have been many hundreds of thousands of papers actually written on this and I categorize these papers as belonging to one of five mechanisms. And these mechanisms are kin selection, direct reciprocity, indirect reciprocity, spatial selection, group selection. And for the purpose of this meeting here I want to discuss direct and indirect reciprocity if I have time a little bit about spatial selection. I'm happy to take questions about the other mechanisms also. So direct reciprocity is the idea I help you, you help me and this was written in an important paper by Robert Rivers in 1971. So direct reciprocity leads to the so-called repeated prisoner's dilemma. We played this game that we just played not once but several times. If we played several times it is no longer the case that the best thing is just to defect if I defect with you in the first round that might upset you and then you will never cooperate with me again kind of. But if I cooperate with you it is costly for me but it might lead you to cooperate with me. So economists can prove a theorem called the Fox theorem that it is possible to find cooperative Nash equilibrium in the repeated prisoner's dilemma. But the question is how does one play this game? And this question was asked in an important study by a political scientist at Ann Arbor University in the late 70s, Robert Axler wrote. He said let's have computer tournaments for playing this game. So people sent him computer strategies to play the repeated prisoner's dilemma and he evaluated them. They paired each other up and then he announced the winner. And the amazing thing is even though many of the entries were smart strategies that tried to predict, that tried to deceive in two consecutive tournaments the simplest of all strategies won and the simple strategy was a three-line computer program sent by game series Anatole Rappaport and it says it's tit for tat. So I start this cooperation and then I do whatever you did last round.  You are playing yourself once removed because I do exactly what you did last time. And that strategy at that time was considered kind of a world champion in the prisoner's dilemma but it has a problem. It has the following problem. If two tit for tat players play against each other and there's a mistake one by accident defects the other one will hit back and this endless cycle of retaliation destroys cooperation. So tit for tat is unforgiving but to do well in a world with errors which was not in Axlerot's tournament but if you want to think about a realistic world where people make mistakes you need a mechanism for forgiveness and tit for tat doesn't do that. So in my PhD thesis I had natural selection run a tournament on the computer and in mathematical analysis and to analyze what is happening if we put it into a context where errors are always occurring and not where we play arbitrary strategies sent by people but natural selection chooses in spaces of strategies. So I start with a random ensemble of strategies. The first thing that you get is always defect. So if people play randomly the best thing is to defect. But fortunately for my PhD thesis it wasn't over here. Something interesting happened tit for tat came in and you can actually prove that tit for tat is a very good catalyst for the emergence of cooperation. It is a harsh retaliator which you need when almost everybody is defecting to get some small cluster of cooperation going. But amazingly tit for tat was immediately replaced by another strategy and that other strategy was generous tit for tat. There's a formatting problem here. So generous tit for tat replaced tit for tat immediately and what is generous tit for tat? If you cooperate I will always cooperate but if you defect I will still cooperate with a certain probability. And that's also a recipe how to save many marriages and the kitchen counter at home you have dice you roll dice and then you decide whether to forgive or not and that would be a stable kind of because you need a probabilistic strategy because a deterministic strategy could be exploited. So this is a mathematical model for the evolution of forgiveness. But the interesting thing that happened next is if everybody here plays generous tit for tat and I play always cooperate I have no disadvantage because everybody is nice and I do never ever retaliate. But that doesn't matter because nobody exploits me. So this is now what is called in biology random drift. I'm a neutral mutant. But there's no pressure for this generous tit for tat like strategy to be maintained. Random drift eliminates it and brings it to always cooperate. It's like birds on an island without predators lose the ability to fly. A biological trait has to be under selection pressure to be maintained. So with drift to always cooperate but you can guess what happens next. You invite the invasion of always defectors and you have a simple mathematical model of human history and people have written books on such oscillations between war and peace. But the interesting thing in all my work on evolution of cooperation over the last 20 years I always find oscillations. Cooperation is never stable. There is no stable equilibrium. How much cooperation you get in a system depends completely how long you can hold it and how quickly you can rebuild it after it has been destroyed. And that's what you need in human society. You need structures that rebuild cooperation quickly after it has been destroyed because you can bet on it that it will be destroyed. It will always be destroyed. And these oscillations we also see in the oscillations of the financial system for example. There is a simple rule and I like simple mathematical results. So this direct reciprocity allows evolution of cooperation if the probability of playing another round is greater than the cost to benefit ratio. So the overall mathematics is complicated but there are some simple rules occasionally emerging. But let me go to indirect reciprocity because maybe that's even more important for the context of this meeting. So this is a Vincent van Gogh painting of the Good Samaritan and we don't really know the motive of the Good Samaritan to help this person but presumably he was not thinking oh this is the first round of a repeated prisoner's dilemma and I should better cooperate here. Instead the Good Samaritan helps and maybe the Good Samaritan thinks I help you, somebody will help me. You know if I'm in such a situation somebody might help me. So how do we get indirect reciprocity to work? If you can assign a reputation to the players. So here player A helps B and then the reputation of A increases. Or A does not help B and the reputation of A decreases. So then you need natural selection to choose strategies who based their decision to help on the reputation of others. So here we need mechanisms that assign reputation. And the web is perfect at doing such things and these reputation mechanisms come in eBay auctions and in buying and selling relationships. So there was, this was a theory that I worked out with Carl Sigmund in the late 90s and the experimental confirmation was published in 2000 where people did experiments with students sitting in front of computers and defined that people help those who help others and helpful people have a higher payoff in the end. What you need for indirect reciprocity is gossip. So people there's some action going on between two people others observe it and then gossip spreads it in the population. And empirical observations suggest that humans are obsessed with gossip. We are talking about others. We are talking with others about others. So people have done experiments in British trains going up and down listening to what people are talking about. I don't know if that's kind of legal. You know about 60% of these topics were about indirect reciprocity in a certain sense. So the very interesting thing is for perfect mechanism of indirect reciprocity you need human language. So the human history you could argue that this was the selection pressure that led to social intelligence and to human language because you need to understand who does what to whom in a social network and you need to be able to talk about it. My friend David Haig here at Harvard said beautifully for direct reciprocity you need a face and for indirect reciprocity you need a name. So there's a lot in our brain that is just there to recognize faces and read intentions into faces and try to understand what people might be doing but that's not enough for indirect reciprocity. For indirect reciprocity you need to be able to talk about others and that seems to be a typical human characteristic. Again, there's a simple rule here and this is that natural selection can favor cooperation by indirect reciprocity if the probability to know someone's reputation exceeds the cost to benefit ratio. So you need mechanisms such that interactions are not completely anonymous. If interactions are completely anonymous you run into a problem. But you also run into a second problem and this is that the assignment of reputation so to say the gossip itself has to be a game that has to be conducted honestly. So this is on a higher level a cooperation defection problem which is rarely studied. Almost over. So then spatial selection is just the idea that neighbors help each other so you get cooperation emerging if cooperators can form clusters and then clusters of cooperators can prevail against defectors. And this is something we study on graphs and we have studied this on all sorts of networks random regular graphs, random graphs, scale-free networks and to our great surprise we found a beautiful simple mathematical rule that this graph selection favors cooperation if the benefit to cost ratio is greater than the average number of neighbors. So this spatial selection works if you have a few close friends. If you interact loosely there's a very large number of people that it's much harder for that mechanism to work. Something else with this evolutionary set theory where people belong to sets they interact with others in the sets and they join successful sets and that is also something that leads to the right spatial structuring that can be a powerful mechanism for cooperators to find each other in sets. So you hear about groups that work well together and you want to join that group and that can be a powerful mechanism. The five mechanisms I discussed, three of them and there are simple rules for all five of them and these are the cooperators in my group here at Harvard and recently I wrote a book called Supercooperators where I summarized some of these ideas. Thank you very much. Question for Martin while Nicholas is setting up the slides but with the spatial selection one way of thinking about that there's I think it's actually I think it's Dunbar's work to gossip on trains and that brings in a whole other issue around privacy which is the notion of networks and our technologies making it possible for us to have much larger networks of stronger ties. So when you said that a that the larger networks didn't have the same level of cooperation was that because they were larger or because they were weekly connected? So what we call a well mixed population is a complete graph where everybody interacts with everybody else equally strongly and this does not provide selection pressure for cooperation. What you want is that you have a few connections with people and then these are cooperators but there's a very interesting trade-off because I can achieve it by saying one friend and we will cooperate and we can never be exploited but then if there's somebody else showing up you know I could increase my overall income by also making this connection and so we build a bigger network and what we found in a recent study is that the network as it becomes bigger and bigger generates more and more wealth but becomes more and more vulnerable to the exploitation of defectors and at the point where the defectors can destroy it you have the largest wealth. So it's a trade-off between wealth and stability.


Hi, my name is Jody Baker and this lecture that you're about to watch is produced using Firefox and ScreenFlow which is a video capture tool and I'm recording on a blue Yeti microphone. This video lecture will walk you through the steps for embedding a direct link to full text articles from one of the library's electronic resources into your Moodle course. You've probably been struggling with the need to comply with university copyright policy and the law on the one hand and the more immediate practical challenges of teaching and delivering resources to students in the most efficient way possible and trying to keep it as simple as possible. As Emily Carr and other campuses begin to phase out the traditional course pack and we all know how onerous the process of putting together a course pack has become in recent years but more and more we're going to rely on delivering resources like readings, images and video to students online and we've all been uploading PDF files of our readings and JPEGs of images we're working with because it's the simplest and most efficient way to get material to students and uploading PDF files is really easy and really simple but actually complying with copyright has gotten a lot easier and I'm going to show you how to link to articles in a way that complies with copyright law. It's just as easy as uploading a PDF file. Now book chapters, they're a separate issue and the policy there is to simply ask permission of the author and word on the street is that you will get permission nine times out of 10 so just send the author an email and ask for permission to use a chapter from his or her book in your courses. In order to ensure that you are complying to copyright law and the license agreements that Emily Carr has with our electronic content distributors you are required to embed links to content rather than an actual PDF of the article. So first you have to become comfortable locating an article in an online journal with one of the library's electronic resources and the library provides access to several full text databases. The library's electronic databases are accessible through the library website and are available both on and off campus to all faculty and students. So I'm at the library website now and in my other tab I have the course that you're currently in and I'm going to take two resources from two databases from the library website and put them here in the resources module. So the first thing we do is go to the library databases and you can click on all which gives you access to all the databases and search that way or you can go to a specific database and we're going to go to the art full text so first you'll click the connect button to connect to the database and you come up with a search. So I'm going to look for articles on online art pedagogy and click start. So we have a number of articles and I'm going to get this one preparing art teachers to teach in new digital landscapes. So I'll click on the link and there are two buttons on this page for that article which I care about and one is the citation link here in the corner and the other is click to copy the PDF full text article link. That's the persistent URL or sometimes called the permalink. So first we'll get the citation and in this database it gives you several options for citation and since Emily Carr tends to use MLA I will take the MLA citation and I can just simply copy and then I'll go to the resources page and add a resource. I'm going to add a bibliography as a page and I'll just paste it into the content section and there it is in MLA. So now I'm going to go back and get the persistent URL and I'll just right click this link copy the link location I'll then highlight the title of the article click the link insert link button and paste the link into the URL box. You can have the target as open in this window or open in a new window the decision is yours. So there it is and I'll click save and display and there it is on the bibliography page that I just created. So all I have to do now is click on this link and it will open. So I've retrieved this article and complied with copyright and all my students now can retrieve this article and you're complying with copyright. So it's very simple and very straightforward. I use skim for my PDF reader and I like skim because it's open source and it allows you to highlight and underline text. You can underline text you can highlight text and if it's a PDF that's an image of the text as opposed to the actual text you can highlight using boxes like so. So consider using skim as an alternative to Adobe Reader. Returning to the library homepage we'll search another database to find a full text article. This time we'll use JSTOR and we'll connect to the JSTOR database and we'll search for art history online pedagogy and here's the article we want digital culture and the practices of art and art history and here's the web version of the article and we want to click on the view citation link and this gives us both the citation and the persistent URL or in this case it's called the article stable URL. So I'll simply grab this text unfortunately in JSTOR we can't choose between MLA or APA formatting. I'll go back to my bibliography page clicking the edit button. I'll add the new citation and make it conform to MLA format. There now that it's in MLA format I'll return to the JSTOR citation and copy the article stable URL. Again I like the title and drop in the stable or persistent link. You'll notice the URL has the phrase EZ proxy that ensures that the PDF is obtained through the library and through our electronic content distributors. With the JSTOR database the link takes you back to the JSTOR citation where students can then sign in through the library and download the PDF from that page and there it is. So that's how to get resources to your students and comply with copyright policy and law. Thank you.


to constituency, right, everything from former to designers to clear rights and such. And what we're trying to do, of course, is promote the rich, as I said earlier, and create a world-class contribution, thanks to our emails from the city of Dallas and North Texas. So we're really trying to make it a form of this particular area, or the focus on this area. And then, we just have a, we kind of have a living mission. We're a new group, so we're starting to be separate. So right now, we're trying to put together a particular initiative and what we're trying to work with is with the City Council. But the idea that we don't mind being a mission, so we just for right now, we have what I call a tennis mission. There's one that we can live with for right now. And the idea, the focus is the notion of dissemination of new works, by Latino artists, right. So the notion is, and you can read that, is to really enhance this ability, but also to garner a sense of recognition for the work that we do. So, and of course, those two go hand in hand. So we're trying to build a sense of presence in this particular area, because we're here and we're not going away. And then, hand in hand with that, of course, came up with a vision say that is all part of the organization try to do in terms of put out a particular vision with how they, in a sense, see the future in a sense, right. So the mission sort of gets into how we're living in the present, how we're trying to engage with the present, and then our vision sort of takes us to the future, right, or at least some kind of aspirational future. And so we're trying to procure the structural support within the city of Dallas and surrounding cities to fulfill this particular mission. And so what we're trying to do, as a lot of you know, I'm sure you're good at the same thing, we're really trying to key into or work into finding adequate resources, which means funding resources, right, and at the same time trying to find a workspace that we, the enduring workspace that we live in and breathe in and do our work. So those are, as I'm paraphrasing, the vision. So we're trying to engage the mechanism that's already in place that perhaps creates a new one along the way, in terms of how we might enhance our visibility and our recognition in the city of Dallas. All because we want to serve our particular communities. It's not just about us. It's about how we are serving our particular community. So that's the foundation. So I'm sure you have lots of wonderful stories yourself. From your particular words, and we'll get to Dallas in just a second, but we have a little agenda, so now I'll turn it over to Mike. Okay, and you're here. Mary, thank you for coming. Those of you who are ready for the TCT conference, thank you for coming to this meeting. And for those of you who drove from far and wide, we appreciate you being here. The issue of visibility came up a while ago. It was a TCT study a couple of years ago, talking about the relative invisibility of theater in general in Texas, in this area, in Dallas area. Not going to be going, probably, well, if Texas mainstream Dallas theaters were relatively invisible within the broader future, we're about Latinos. Well, we were really, really invisible. So that got me going, and I was able to publish an essay in a volume, Theater and Small Nations in England. Very interested in ethnic work. And that got me going to thinking about how many companies we are here and the work, the Latino work that we do here. So that got me thinking about visibility in terms of, because I'm a scholar, basically, primarily. So visibility happens when somebody writes about your work when your work is printed, when you are catalogued from the library. It's great to have performances. It's great to have unique reviews to validate your presence. But you also need to be in academia. Your work needs to be part of the canon, and it's not going to be part of the canon if it's not published. People can't find it. And most of the time, it's, oh, we love to hire Latinos or have Latino play, but we don't know where to find it. What we want to do is have an anthology of works created in Tejas, and we're calling the volume Made in Tejas, of works by people who live and work here from the piece that we are asking that the piece be produced between 2000, year 2000 to now, so it's relatively new work. And we're actually going into three different kinds of works that we are interested in producing. I mean, in publishing. One is regular plays, one-on-play, school plays, one-on-locks. It works by companies and or individual artists. The other is Theatre for Young Audiences, which is usually left out or done separately. And we're going to have a third component of devising work, work created collectively. So there's going to be an engagement between the critic, a scholar who writes about the process and the company. In all of the sections for all of the participants, there's going to be a Q&A so that the writer speaks or the artist speaks. We're all asking all artists to join us on certain issues, so there'll be the voice of the artist, and then at the end, Tommy's going to be talking about something that she's been working on, too, that we want to include in the end quality. So please spread the word. We have a deadline June. We want to work hard on this fast.  We want to work hard and fast so we have a deadline of, is it June something? June 26, but we're willing to be flexible if we have work that's coming down the pipe. By the way, there are three curators to this. It's Lorenzo and Vanessa, where are you? Vanessa, Mancala Taylor's working with us and myself, Alfie, I'm also curating this. So that's for the plays and creative work. The other thing that I'm concerned about is you're locating, and if you can help us, locating scholars that are working in your particular areas, recording the history of the works that you do. Like, for instance, Jorge Huerta just came out here a couple of months ago, and he shared with us the activity of the LA Alliance, and they have three scholars working with them. It's Lorenzo and Jorge, Tiffany and Lopez, and Jean-Claude. They have three scholars working in the LA Southern California area to go to plays, to review plays, to see the state of, to report back to the major alliance that we're all forming nationally. So it would be really cool to have the data in your particular areas, often in San Antonio, in the valley, to locate and identify scholars who are working on the history of your work. What's going on there? So we have another volume on the history of Texas Theater. There's really a lot of interest in that. Publishers are there. There's no history of Texas Theater, right? It doesn't exist. And if you read the books that were published by after Google Press back in the days, when Nicolás Canelo was publishing a lot about Catholic history, it stops, sorry, folks, it usually stops in San Antonio and maybe Austin. It doesn't go anywhere in the world. So basically, there's just a partial, very fragmented history of Hispanic Latino, Chicano Theater in Texas. And so we're working to build that. So if you can help us with that, that would be really great. Does everybody have a call for submissions? We'd love to hear from you. Spread the word. Thank you. Probably one of the questions. I didn't do that at the beginning. I thought about it. Introduction. Who is that guy? We don't know. And I'm usually a little bit of a performer, so I usually do a little of something. But yeah, I just jumped in. So I'm going to go to Garcia, an department chair in English with North Texans, right up the street, right in Guine, Texas. And I'm going to sit back and I'll leave. To Nicolás Canelo. And I'm actually in the department world, in Spanish, so I teach Latin American and Latin and theater in Spanish, but I read it in English. And for those of you, this is thanks to Cora-Benguin on the door of places like Theater Jones for a long time. Theater Jones is an online performance review venue. Theater with a TR, Theater Jones. And they just hire me. Hire me. Nothing. I'm a first Latina or Latino by Latinos and Latinas. So they also are interested in interviews, question and answer, you know, articles. So if you ever have any work that you're interested in coming up with, we end up doing some kind of collaborative thing. You know, there's a venue to promote that online. So that's really kind of a cool thing. And maybe we can start off by just having the people who are in Tanto who are here today, Tanto members.  Are you the only one? No. So can you introduce yourself quickly? Dave Lozano, kind of me a theater company. Rod Betts and Diploris, also kind of me a Lozano. No, Lozano. Lozano is called the Taylor director and a company member of the kind. And the other part of the service is actually Florida. And my name is Florida. So maybe we can go around really quickly and maybe you can decide who you are and then if you're an individual artist or a company that you're interested in, we'll start here. Yes, please. Good afternoon, everybody. Yes, Lozano is a producer and also they've done a workshop at Texas. We've been around five years and we've been doing this with Loretta and Loretta for a really long time. I'm Loretta, I'm just a director of the Afro people. I've lost to Texas. And what are the founders of the company? I'm Joanna. And you are the I don't know anything that is behind the curtain. I'm Molly Ortiz. I am an actor, playwright and spoken word poet. I am working at my master's at UT Phan Am in the lower Rio Grande Valley. I'm a playwright and actor, musician, recording artist. And I just founded the Apropato Lito multi-cultural theater company because we don't have a professional theater company. So a freelance actor a former soloist a former writer of commercials and also a workstout from San Antonio. Latina Latina Theater. Hello, I'm a theater artist, director, playwright, producer, cultural worker and oh my god. I'm Joelle. Settles for the theater arts program director at SASE I lost to a theater company and a southbound member as well and an actor and a Japanese show I'm Roxanne Sugar-Aque and I'm a professor at UT Austin but I'm also still in my water. I'm a playwright and a scholar and a proud member of SASE My name is Marcy McBan and I'm a Latino literature specialized in theater and trying to get more theater performance, Latino theater performance in our community I'm Latina My name is Jack Hargis I'm a student and I'm an intern and a director I'm Rafael de Maia I'm an actor a pop artist I work with a theater company and I work with Deftal Dallas and to create networks communication so, Megan she'd like to talk to you all about it and then we'd like to ask Rupert to share a song with me as we talked about a couple weeks ago when I was down in Austin so it was like a great opportunity so maybe it was that time I just proposed and indeed I created this volume and we have already discussed whether it's going to be volume one of a series of Latino and Chicano produced works from Texas based artists I thought well in order to get the word out to the people who need to see this call for submissions we need to come up with a mailing list to email this and then I thought well where is that document you know it's nowhere it's not on the internet, it doesn't exist yet and I thought well I'm trying to live as an elder by that idea that we are the ones that we have been waiting for so I'm the one that's doing that creating that list, that searchable database that will be shared publicly and reciprocally with anybody who wants to see it and so volunteering to just step up and create this spreadsheet with just your names and if you're at Texas based playwright Roxanne you're on the list there were people who came to mind immediately Rodney because I know your work today that we're the reason why Texas the Chicano Latino theater alliance seemed to be already moving very quickly and getting on the road on the path according to our mission and agendas, it's because we already know each other, we're migrant art workers a lot of us have traveled to and fro and my name is Celana based in San Antonio previously recited and worked here and I lived in Austin for ten years which is where I met Rodney Rodney is now in debt and so we're migrant art workers and so we already know each other we're already networked in but in terms of this document that's playwrights, Texas based previously produced works I haven't seen that document yet I'm happy to be creating it because it gives me reason to get in touch with all of you again and reify and update my knowledge my information about you what you're working on now and every time because we're sharing caring group of people in our community that we act like familia as soon as we meet each other any time I reach out to Rupert and he was in the middle of your festival you knew play festival and right away he said here's names of some playwrights and then mere days after the end of the festival he had the emails to email addresses of these people that's how we work that's how we care and thank you Rupert for that and so the list is growing we have over 65 names and there's more coming through I'm very very happy about that and the added bonus of this is this document is going to be included in the form that we're producing so it will be a nice appendix to what Vanessa and Lodance are going to put together very exciting so please get in touch with me if you have anybody to suggest I will do the digging and contacting I will reach out to these folks if you can just give me the contact information be it a phone number, email address is preferable I'd rather not do everything through Facebook there's been way too much time on that but a private email is preferable and the sooner the better of course because I want to be sure that we get the call for submissions out to as many folks as soon as possible and TamicoMexican.com is one of my email addresses that's permanent Tamico is a cool pool where you can just playwrights designers, directors, or who-all is the base of this is already turning into a part-time job that I'm not going to take just to do the playwright because I want to do it right I'm too old and I don't want to do things you know, have you know, cocked or whatever the two of you have so I want to be sure to be as thorough as possible with this and I'm a playwright as well so I want to know who my homies are so that's right and as far as the information aspect of what I feel part of my agenda, my mission is the member of Tanto and any Latino-oriented theater group in the US is that we are all living breathing archivists of our work and so we may not have yet the publication that y'all are going to create we may not have yet this database that I'm working to create but we all have information all living breathing archivists so I challenge you to keep those up wherever your notes are in the shoebox or in a data file or in a junk drive and because we're getting so activated we're probably going to need that material in some form or fashion be it with a blog or a searchable databases on a website that we create who knows the sky's the limit as they say B.V. Olguin, Ben Olguin is a scholar who's writing about the work of great bodies and Devo Paredes and E.T. Austin is also one of the best I would mention Thank you Ways of networking and sharing talent and ideas within the different alliances and we even started a conversation with this about people who love to tour and we would love to bring other groups in that or touring and one of the things that we run into is not knowing who's out there and also not knowing who to contact we do get asked a lot to go tour our shows are not designed that way we design shows for running for three weeks in the theater and they're too big to move and if we knew we were going to be moving we could design for another space and we could also then take that theater that same show and move it off to another city now that's the big that's I mean so obviously whenever I start touring tomorrow we're going to have collaborations and working together we're going to have marriages and you don't start a relationship by starting a production you know you have to get to know each other what are the best ways that your company can help my company and your company can help out but one of the things that we've talked about a lot and maybe I should call it the Rodney Bars Initiative because he's already doing it to some extent and that is we find that a lot of our players and a lot of our directors have really not gone off and learned they've basically been doing the same thing for us for 12 years and so it's sort of like how do you get new talent new blood so we talk about maybe just bringing in a director and I know the director Houston, Centennial Fort Worth, Dallas, I don't know where else probably but just again I've seen this work in almost every one of those cities so the idea is how do we network so that we can bring that new blood into Austin State and there's a wonderful thing in Austin called Viewspot Festival I don't think you've heard of that festival or not if you get a chance to participate or see some of that it's really wonderful because they bring talent from all over the world from South America to Amsterdam just coming in I think to the next where they're trying to get all the eases and stuff but you'd be amazed at the information or the things that people are doing in theater like in Europe and stuff that we don't see here and I just wonder what's going on in Dallas it's going on in San Antonio it's going in Houston up in North Texas and all ended in and maybe by exchanging like just the directors we could do something similar to they bring a play that they've already progressed the idea that they've already directed they've already worked so they're making a big introduction to Austin or Austin going to San Antonio so you're not reinventing that whole production it's already been done in one place to bring it it actually kind of cuts down on the time and design and again these are just all fantasies these are all ideas we're just going out and stuff I'd love that we're getting a list of playwrights because we get asked to a lot and we do a playwright festival we get submissions of scripts and so we get quite a lot of playwrights they go through a process of being read and produced almost every one of the plays that we've done are writing on paper including Money Action Girl which we just finished up a great successful run for that which is coming into Dallas so one of the things that we would like to do though I've learned that I've known Kodak for a long time that I've never seen one of your play I've never been to Dallas in play you know I mean it's yes, we actually did it commercially years and years ago and I know you've come to Austin years and years ago you've been to Austin you've been to Austin so some of these things have happened but they've been lost and forgotten we did a little bit of a collaboration we were at their space basically the same production we had in Austin we took it to your space the same set, the same costumes I'm not saying for life and design but we brought the base of the same play with all the same cast and worked up it under the auspices of adagro productions which is in San Antonio too I've seen people have heard so what I would like to propose and we do have a great adagro the first step might be to see other shows and at that moment we have to travel to Dallas and they need to care about it and come see a play and then stay another day to actually kind of talk at coffee talk about production talk about what they should be in the future just a very formal conversation San Antonio is so close to Austin it's an hour by car now we can make 80 miles an hour until we get the shows so these are the kind of things we would like that Austin and Seattle View was interested in giving this informal context the vision of talent exchanges new plays maybe even a touring circuit that's why I'm trying to see a touring circuit in Austin that goes from Dallas to Austin and San Marcos and now it has some programs that are happening in San Marcos San Antonio Vallejo it's going to be far away but when you hit San Antonio right in the middle of the valley the old valley filled with the town and our engine and ground building up through Kingsville and Corpus so there is a circuit that exists that we don't have to travel real far but that's a real place a big fantasy might always be able to take off and do that kind of thing and knowing that there's a group there that's already going and helping promote because that's what we don't need to tour all the promotion and everything we've gone to a gallery and had two different experiences one we had a great promotion and did a show another one we had a terrible promotion we had 10 people in the audience for two shows so that's the kind of thing you don't like happening so the conversation that I think is really important I don't think we have a very good group and then do some other things there's certainly a website that's our idea idea I want to see what's happening and think about it we have a very good group we have a very good group we're all welcome to join TANTO but we have talked about the idea of creating a central website with links to works by other so yeah that's definitely on our to-do list absolutely I want to share with you the resources we have in order to help jumpstart these types of collaborations and as I told you we have an event called Limonadia which is one night one each night at night it's always the second Saturday in March it's an open call that we have I've started out in the theater and recording committee for three, two years and it's going to be my third which is some massive explosion of theatrical proposals there was one proposal that was a solo artist from Spain he was oh let's take him it's a locally produced performance that we have over 300,000 people in 10 and there's one thing there already in place that's supported through an infrastructure that's supported through the mayor's office so the open calls have been very good so there's artists that are staying so the thing about planning the proposal it was like he asked for like $1500 we're like he's in and then so at that point he had to revise his proposal he said oh I forgot I have to bring my tech person and then he's like well you said $1500 and that's what we need to keep you can't come with $1500 I mean that's like isn't that like being wonderful to travel with like somewhere in Texas you can just come on down after the performance so the open call for that is going to continue to happen in December so not only I think a local theater you at least need to apply right now it's not that you can go to and then you apply online it's really easy you ask for the money that you need and then you don't ask for more labor you know artists we have to cut ourselves you know this type of thing is like a good way to like if you have a project that could travel that sort of might work in an open space so we have paid as well but just like for one night we have resources and you're guaranteed an audience like we're guaranteed you know 300,000 people so let's use that resource to like freak out like San Antonio like you know mainstream theater and say oh my god you know we got like 40 the after-applicants that would freak them out you know this how about that how about this it's creative as soon as the information is out I will forward that information and that is one way continuously like you know we have funding for that you can be considered through a jury curated thing but that's what needs to get you to San Antonio okay is there like a time limit on this because I know in the past it's like 20 minutes for performances that's still like one act depends but you need to think of like this particular event is primarily outdoor there's more theaters as well but more like public space if you have something specific outside that might work or if you want to come in maybe it's an excerpt the thing about it needs to be new work so it can't be anything that you know we want like that you know work that's in a site you know San Antonio I don't think San Antonio is any more about I think like since it's curated that probably goes into their decision right because they can't have one act can we do this can we have many not piece of paper over there like the website or the website or whatever you know resources and websites that we already have we do so that we don't have to worry about Johnny downing it that place would be the place to post and if you want to break out smaller groups we've got but it seems like we're kind of working how would you like break out into smaller groups by interest by what you do of playwrights which is after which is company or by geography area based on maybe talking what do we most say in collaboration collaboration is great so we have great cooperation we have are there others who are a new center yeah we have a new center let's do the same let's reverse the name individual artist okay so we have three and then we put up identify what is important to you right on the sheet over there and here we have also


Introducing, the Daredevil's of Hollywood. Good to see you, Mr. McKay. Yeah, and look, Bob, I'd like to get this on the first take. All right, sir. Now let's see. I'm supposed to ride the motorcycle right through the board fence and then crash into the house. Is that right? That's right, Bobby. The back of the fence has been sought almost through, so it'll break easy. Okay. Well, here I go. I'll stand by for your signal. All right, everybody, this is it. Really making speed. This is gonna be good. Making true life experiences of those men behind the scenes. Those daring unsung heroes whose breathtaking adventures on the screen have thrilled millions.  Those men who complies the strangest fraternity on earth. The Suicide Squad. The movie Stunt Men. The Daredevil's of Hollywood. Ladies and gentlemen, in bringing you this copyrighted radio feature, we have presented in the past some of the ace stunt men of Hollywood. But now we have a genuine surprise. We are privileged to have again as our guest a stunt girl of the movies, Miss Ione Reed. It is through her cooperation that we are able to re-enact some of the highlights of her dangerous profession. The thrilling scenes you are about to hear are her own actual experiences. Miss Reed is here in the studio right now. And later in the program, we will bring her to the microphone.  As the brilliant California sun peeks over the horizon to light another new day in 1929, we see throngs of men and women walking briskly through the massive gates of Emotion Picture Studio. Drivers of automobile stop long enough to be recognized by the policemen on duty. Then they too hurry into this city of wonders to take their places in the vast machine. Personally, a sleek high-powered roadster pulls up to the gate bearing a beautiful young girl. She is dressed in sport clothes and her smooth blonde hair blows gaily in the breeze. She is immediately recognized and admitted. And a few minutes later, we find her in the office of Mr. James Swanson, a director. Well, I'm not late. No, no, not at all. We probably weren't you sure seen until about 10 o'clock anyway. Well, tell me, what am I supposed to do? Captain's office didn't tell me much about it over the phone. Frankly, Ione it's a very dangerous stunt. I wouldn't want to trust anybody with it but you. But I honestly feel that you can do it. It has something to do with trains, doesn't it? Yes, you're riding on top of a freight train with two men and the breakman gets after you.  I see. How fast will the train be going? About 18 miles an hour. Oh, well, Mr. Swanson, that's very simple. In fact, there's nothing to it. Yes, but here's the dangerous part. There'll be a passenger train coming from the opposite direction on the other track.  How fast will it be going? Tell the truth Ione, it'll be wide open. Oh, I see. That does complicate matters a little, doesn't it? You see, it'll have to be close to look good. We're spending a lot of money on the scene, so I want it done, you know, successfully. That's why I had them call you. Okay, Mrs. Swanson, we'll give it a try. After all, we've done some just as difficult. Fine, fine. I knew you'd do it. In the San Fernando freight yards a few miles from Hollywood, workers from the studio have been busy since daylight preparing the location set. Everything is ready for the big scene. Miss Reed and the two stuntmen have planned the stunt out to perfection. Every movement has been carefully timed and checked. But even veteran cameramen and members of the crew who have witnessed hundreds of dangerous scenes are not able to conceal their nervousness. A loss of balance, a slip, a misstep will result in certain death. The freight train stands on the track. It seems to breathe like a living thing, healing to the tenseness of the situation. While far in the distance, the passenger train stands waiting for the signal. Thank you, I'm Miss Reed. I guess we're ready. How about it, boys? We're all set, Ione.  And stay close behind Carl as you can. The three of us will run across the track in front of the passenger train one at a time. And I'm supposed to be last. Well, what's the holdback? Let's get going. Okay, here we go. All right, everybody. Come on, boys. Let's get it over with. Ready for cameras? Okay, Mac, go ahead. I'm right behind you. When, through her miraculous quick wit and calm, cool thought in the face of great danger, Miss Ione Reed was able to walk away from that scene unhurt.  It is with extreme pleasure that we present this courageous young girl interviewed by Hell Style. Well, Miss Reed, my curiosity is still very acute. Tell me, how on earth did you get out of that tight spot? Well, when I fell on the track, I knew I didn't have time to get up and run, so I just rolled. Just made it between the two trains. Must have been very close. Certainly was. Those trains looked as big as mountains. And did you just lie there until the two trains had passed each other? That's right. Of course, that wasn't the way the story was supposed to be, so we had to do it over again. You mean you had to actually do that dangerous stunt twice? No, not twice. We had to do it five times. Something went wrong every time. Did we finally got it right?  Incidentally, it's almost amazing that such an attractive girl as yourself would be in this dangerous business. It's a good thing this is in television, and maybe you wouldn't say that. I certainly would, and television would prove it. I only wish our listeners could see just how attractive you really are. Thanks. That's very nice of you. Now, tell me, how did you happen to get into the stunt business? Well, I used to play leads in western pictures. There were always some kind of stunts to do, and I always did my own. Most of them were horse stunts.  I see. And one thing led to another, and finally I was doing all kinds of stunts. I suppose you've had quite a lot of close calls, haven't you, Miss Reed? Yeah, I have. Have you ever been injured? No. No, not seriously. Just a few ribs broken. My nose was fractured once when I was doubling for Clare Ball. You probably remember the picture, Carla Savage. Yes, I remember it very well. They called me out on location. I didn't even know what I was supposed to do until I got there. I walked in on the set and... Oh, pardon me, Miss Reed. We'll learn what happened in just a moment, but this is where we hear from our sponsors. All right, Miss Reed, now carry on. Well, when I went on the set, they were waiting. Are you ready? All right then, Miss Reed, we're ready for your scene. Now you just ride that horse up by that rock over there and when the horse sees the snake, he'll rear up and... Wait a minute. Who's going to ride what horse up to what, Snake?  Oh, hold on. Listen, Mr. I don't like snakes. They're out of my lawn. Maybe you better get somebody else. Oh, we can't do that. I own. You're already made up for the part. You're all dressed. Oh, it'll be all right. I'm sure it will. But I still don't like snakes, and I have no reason to think they like me. Now look, I look here. That's a 10-foot rattlesnake, but he's harmless. You see, they extracted his fangs. He can't hurt you. Oh, no. He can scare me to death. I like it. I... But I'll do it. Ha-ha, fine.  That's all there is to it. What do I do? Fall on top of the snake? No, but fall as close to him as you can. Okay, I still don't like it, but here you go. Okay, everybody. All right, places, this is a take. Don, we'll take you to the hospital. Is this he now? Okay, if that's the way you feel. All right, we'll take it. Ready, everybody? Well, Miss Reed, that certainly was exciting. But if the snake was harmless, I don't suppose you were in any great pain. That's the funny part of it. I found out later that the snake was as deadly as any rattlesnake. His fangs had not been removed. After I fell off the horse and ruled out of the way, Clare Bo came into the scene and actually killed that snake with a riding whip with a wonderful shot. It certainly was. I remember it very well. And how about your nose? That was very painful, wasn't it? Yeah, it was. But in a way, I didn't mind so much. I'd wanted a new nose for a long time anyway. And here was a chance to get one on the house. Well, that certainly was an optimistic viewpoint, Miss Reed. I can truthfully say that you have more spunk than any girl I have ever met. We have enjoyed your exciting experiences more than we can possibly say. And on behalf of our listeners, I want to sincerely thank you for coming here. I know that everyone joins me in wishing you the very best of luck. Goodbye and thank you again.