How to Select a Microbiology Contract Testing Laboratory? Tony Cundell, Ph. D. Microbiological Consulting, LLC Scarsdale, New York

Transcription

1 How to Select a Microbiology Contract Testing Laboratory? Tony Cundell, Ph. D. Microbiological Consulting, LLC Scarsdale, New York June 13, 2017 IVT Microbiology Week 1

2 Presentation Overview Rationale for outsourcing your microbiological testing Selection parameters Pre audit questionnaire Audit objectives Difference between a business contract and a quality agreement Important issues in building the relationship Method validation/suitability testing 483 observations Failure investigations Response to FDA Quality Metrics program June 13, 2017 IVT Microbiology Week 2

3 Microbiological Testing June 13, 2017 IVT Microbiology Week 3

4 Benchmarking Questions Who in the audience works for companies that have outsourced routine microbiological testing? Is it a trend that is growing in the pharmaceutical industry or not? What was your experience with the process? June 13, 2017 IVT Microbiology Week 4

5 Rationale for Outsourcing Today, while the need to innovate remains more strategic and imperative than ever, it is no longer the case that routine laboratory testing support need be. Outsourcing laboratory functions to a dedicated, independent, third party service provider can not only deliver savings and strategic commercial benefit to a manufacturing company but also increase corporate market agility for responsiveness in today s fast moving and global market place. Eric Creveling, Director, Whitehouse Laboratories, Princeton, New Jersey June 13, 2017 IVT Microbiology Week 5

6 Rationale for Outsourcing Outsourcing has been widely employed by the pharmaceutical industry to improve efficiency and reduce costs. The most commonly outsourced CMC activity is analytical testing. This market is growing at a fast pace: the global healthcare analytical testing market is projected to expand from $2.42 billion in 2016 to $4.13 billion by 2021 at a compound annual growth rate of 11.3%. Major areas of testing stability testing, raw material testing, method validation, microbial testing, environmental monitoring, physical characterization, batch release testing, and bioanalytical testing. June 13, 2017 IVT Microbiology Week 6

7 Rationale for Outsourcing Microbiology managers, supervisors and analysts should ask themselves, what value do you bring to your company, are your activities considered part of the core competencies of your company, and can your services be better obtained at a lower cost by outsourcing these activities? The reality is that the ability to do routine microbiological testing, even when done well and in a timely manner, may be insufficient a contribution to your company to have strategic value. June 13, 2017 IVT Microbiology Week 7

8 Benchmarking Questions What are the most value added activities that microbiologists can bring to a pharmaceutical company? Method development and specification setting Microbial contamination risk assessment CMC Section drafting Validation of sterilization and depyrogenation processes Microbial contamination investigations Drafting replies to regulatory findings Product release and stability testing June 13, 2017 IVT Microbiology Week 8

9 Outsourcing Models There are three different outsourcing models: Fee for Service Analytical work performed at the contract testing laboratory. On site Leased Microbiologists Contract or temporary staff nested in your laboratories supervised by your management. Technical In sourcing Services Dedicated facilities, equipment, and personnel within your facility with project management, supervision and analysts supplied by the contract testing laboratory. June 13, 2017 IVT Microbiology Week 9

10 Downside to Outsourcing Microbial Testing Stripping out expertise in microbiology from your organization Loss of a department that recruits entry level staff to your organization Less emphasize on microbial contamination risk assessment, exposing your company to serious business risks Loss of hands on experience in testing products Additional hand offs during release and stability testing, data review and failure investigations Exposure to greater compliance risks Danger of loss of intellectual property June 13, 2017 IVT Microbiology Week 10

11 GMP Regulations Why must we conduct release testing: Laboratory testing, which is required by the CGMP regulations and , is necessary to confirm that components, containers and closures, in process materials, and finished products conform to specifications, including stability specifications. General CGMP regulations covering laboratory operations can be found in 21 CFR 211, subparts I (Laboratory Controls) and J (Records and Reports). June 13, 2017 IVT Microbiology Week 11

12 GMP Regulations These regulations provide for the establishment of scientifically sound and appropriate specifications, standards, and test procedures that are designed to ensure that components, containers and closures, in process materials, and finished drug products conform to the established standards. Section (f) of the CGMP regulations specifies that finished drug products that fail to meet established standards, specifications, or other relevant quality control criteria will be rejected. June 13, 2017 IVT Microbiology Week 12

13 GMP Regulations How do these GMP regulations effect contract testing? The responsibility of a contract testing laboratory in meeting these requirements is equivalent to that of a manufacturing firm. From 2006 FDA Guidance for Industry Investigating Out of Specification (OOS) Test Results for Pharmaceutical Production June 13, 2017 IVT Microbiology Week 13

14 Presentation Overview Rationale for outsourcing your microbiological testing Selection parameters Pre audit questionnaire Audit objectives Difference between a business contract and a quality agreement Important issues in building the relationship Method validation/suitability testing Failure investigations 483 observations Response to FDA Quality Metrics program June 13, 2017 IVT Microbiology Week 14

15 Lab Selection Parameters Important selection parameters for a contract testing lab include: Technical reputation Compliance level as demonstrated in external audits Access to routine and specialized testing procedures Location Scheduling Opportunity to develop a partnership Cost June 13, 2017 IVT Microbiology Week 15

16 Cost Inventory Remember that contract testing costs include the following: Negotiating the contract Managing the relationship Scheduling the testing Sample shipment Method validation Conducting the microbial tests Sample disposal Reviewing the results Conducting failure investigations Monitoring contract lab inspections June 13, 2017 IVT Microbiology Week 16

17 Testing Strategies Two broadly difference strategies are: Moving routine microbiological testing to a contract testing laboratory Outsourcing highly specialized testing that may be conducted infrequently to a contract testing laboratory June 13, 2017 IVT Microbiology Week 17

18 Benchmarking Questions Who is the audience has participated in the selection of a contract testing laboratory? Did you participate in the audit of candidate contract testing laboratories or not? Are you a contact person with the contract testing laboratory? What was your experience with these activities? June 13, 2017 IVT Microbiology Week 18

19 Presentation Overview Rationale for outsourcing your microbiological testing Selection parameters Pre audit questionnaire Audit objectives Difference between a business contract and a quality agreement Important issues in building the relationship Method validation/suitability testing Failure investigations 483 observations Response to FDA Quality Metrics program June 13, 2017 IVT Microbiology Week 19

20 Pre audit questionnaire How can you build sufficient information as to the suitability of a contract testing laboratory? Review the lab s website Visit their exhibition booth at a regional or national technical conference Request a customer list Benchmark with colleagues at other companies Conduct a telephone conference Submit a pre audit questionnaire June 13, 2017 IVT Microbiology Week 20

21 Pre audit questionnaire Although requesting that the contract laboratory fill out a questionnaire is no substitute for a site GMP audit, they can be useful in both the lab selection process, and as a preparation for a site audit. Remember it is human nature to inflate our capabilities and even deceive to obtain the business. Be careful. Require that the questionnaire by signed and dated by a responsible representative of the contract lab to ensure accountability. June 13, 2017 IVT Microbiology Week 21

22 Pre audit Questionnaire Request the following information and supporting documents: Summary of the company registration, ownership and financial viability Organizational chart including managing director, laboratory director, microbiology supervisor, analysts, and quality head Laboratory facility floor plan with critical equipment locations Laboratory certifications/accreditations suitable for the North American region, e.g., ISO or equivalent, compliance with 21 CFR Laboratory Records, ISO 9001 quality systems certification, and FDA registration number. June 13, 2017 IVT Microbiology Week 22

23 Pre audit Questionnaire List of microbial tests that can be performed Analytical instrument list for compendial testing of excipients, active pharmaceutical ingredients and drug products Process flow chart (identifying critical stages and points of sample receipt, testing and reporting) Standard operating procedures (SOP) manual table of contents. Out of specification reporting and investigation procedures June 13, 2017 IVT Microbiology Week 23

24 Pre audit Questionnaire Change control Staff educational requirements and training procedures Sample receipt/chain of custody/retention procedures Sample submission form/chain of custody Standard turnaround times along with associated rush charges. Fee schedule for data packets and investigations June 13, 2017 IVT Microbiology Week 24

25 Pre audit Questionnaire Critical facility and equipment service agreements Price list including: test, test method reference, model method suitability reports and instrumentation used Volume of microbial tests conducted annually Copies of recent regulatory inspections reports, e.g., 483 observation forms and their replies. Quality Metrics June 13, 2017 IVT Microbiology Week 25

26 Audit Objectives What does the FDA emphasize when inspecting contractors? The inspectors from FDA thoroughly audited WuXi s quality system during the 5 day inspection of their Bioanalytical Services Unit in Shanghai, China, focusing on scientific data integrity, operation infrastructure, equipment, sample storage, archival system, quality control, and quality assurance. The inspection covered bioequivalence studies for preapproval including method validation and sample analysis and other clinical bioanalytical studies from as a general regulatory compliance inspection. June 13, 2017 IVT Microbiology Week 26

27 Audit Objectives Senior Vice President and COO of WuXi Lab Testing Division, Dr. Jason Liu, commented, FDA has the most stringent requirement on quality and data integrity among international regulatory agencies. We are proud with the result of this audit. We will continue to maintain the highest quality standards, and provide the best in class R&D services for our customers worldwide. June 13, 2017 IVT Microbiology Week 27

28 Audit Objectives Your key objectives when auditing a contract testing lab are: Does the lab have the facilities, equipment and trained lab analysts to conduct the testing? Will the testing be of high quality and completed in a timely manner? Is their testing well documented? Are their failure investigations robust? Should you anticipate any compliance issues? Will you develop a partnership with the testing lab with good communications June 13, 2017 IVT Microbiology Week 28

29 Presentation Overview Rationale for outsourcing your microbiological testing Selection parameters Pre audit questionnaire Audit objectives Difference between a business contract and a quality agreement Important issues in building the relationship Method validation/suitability testing Failure investigations 483 observations Response to FDA Quality Metrics program June 13, 2017 IVT Microbiology Week 29

30 Difference between Business and Quality Agreements Business agreements gives general business terms, defines financial arrangements, designates services to be provided, gives notice of price increases, establishes confidentiality rules, and as contract usually has legal approval. Quality agreements defines working relations in terms of GMP compliance and should be attached to or cited in the business agreement. June 13, 2017 IVT Microbiology Week 30

31 Quality Agreements In November 2016, the FDA issued their Guidance for Industry Contract Manufacturing Arrangements for Drugs: Quality Agreements. In the guidance document it was emphasized that a contract testing laboratory may be viewed as an extension of your Quality Unit. See 21 CFR Responsibilities of quality control unit June 13, 2017 IVT Microbiology Week 31

32 Quality Agreements The FDA recommends that the quality agreements should contain the following sections at a minimum: Purpose and scope of the contract agreement Terms of the agreement, including its effective dates Terms for dispute resolution Responsibility of each respective party, including an overview of the subparts of the CGMP regulations Change control and revision practices See more at: online/news/news article view/ article/3519/#sthash.fllvzh1g.dpuf June 13, 2017 IVT Microbiology Week 32

33 Quality Agreements What is the scope of the FDA Guidance for Industry? The FDA clarified that the guidance applies to any organization involved in processing, packing, holding, labeling operations, testing, and operations of the Quality Unit when it comes to making active pharmaceutical ingredients (APIs or drug substances, or their intermediaries), finished drug products, combination products, and biological drug products intended for commercial sale and/or distribution. See more at: view_features/fdas quality agreement guidance vs emascgmpregulations#sthash.abwrysn8.dpuf June 13, 2017 IVT Microbiology Week 33

34 Quality Agreements The impetus for Quality Agreements comes from several cgmp guidelines published by the International Conference on Harmonization (ICH), specifically Q7: Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients (2000), Q9: Quality Risk Management (2005), and Q10: Pharmaceutical Quality System (2008). The EU s revised cgmp Chapter 7: Outsourced Activities specifically cites the ICH Q10 guideline as a driving reason for the revision of Chapter 7 and the controls therein. June 13, 2017 IVT Microbiology Week 34

35 Quality Agreements What should be included in a Quality Agreement? Names and Addresses of the Two Parties Responsibility Matrix Contact List Microbial Testing List Test Specifications Test Reporting Method Validation/Qualification Requirements Sample Receipt and Retention June 13, 2017 IVT Microbiology Week 35

36 Quality Agreements What should be included in a Quality Agreement? Record Retention Derivations/Out of specification Investigations Dispute Resolution Audits/Inspection Rights Change Control Notification of Adverse FDA Inspection Findings Quality Metrics Reporting Requirements June 13, 2017 IVT Microbiology Week 36

37 Presentation Overview Rationale for outsourcing your microbiological testing Selection parameters Pre audit questionnaire Audit objectives Difference between a business contract and a quality agreement Important issues in building the relationship Method validation/suitability testing Failure investigations 483 observations Response to FDA Quality Metrics program June 13, 2017 IVT Microbiology Week 37

38 Building the Relationship It is useful for your microbiology subject matter expert to be included in the audit team or visit the contract testing lab to build a relationship. The contact persons and their back ups should be clearly established in both organization. The mode of routine communication, i.e., fax, , telephone or website downloads should be established. June 13, 2017 IVT Microbiology Week 38

39 Presentation Overview Rationale for outsourcing your microbiological testing Selection parameters Pre audit questionnaire Audit objectives Difference between a business contract and a quality agreement Important issues in building the relationship Method validation/suitability testing Failure investigations Response to FDA Quality Metrics program June 13, 2017 IVT Microbiology Week 39

40 Method Validation/Suitability Testing For the results to be valid, the USP test methods must be followed and the method suitability testing requirements met. Without meeting these requirements, you cannot claim that the product meets the USP microbial requirements and the FDA approved test. Suitability testing is usually conducted with lots of the drug product and multiple challenge microorganisms and is time consuming and expensive. June 13, 2017 IVT Microbiology Week 40

41 Most Common Microbial Tests USP <51> Antimicrobial effectiveness testing USP <61> Microbiological examination of non sterile products: Microbial enumeration tests USP <62> Microbiological examination of non sterile products: Tests for specified microorganisms USP <71> Sterility tests USP <85> Bacterial endotoxins test APHA/AWWA water testing Environmental monitoring Bioburden testing Microbial identification June 13, 2017 IVT Microbiology Week 41

42 Specialized Microbial Tests Container closure Integrity Tests Microbial Assays of Vitamins and Antibiotics Mycoplasma Tests Strain Typing Disinfectant Effectiveness Studies June 13, 2017 IVT Microbiology Week 42

43 Benchmarking Questions What microbiological test does your lab outsource? Microbial identification? Strain typing? Mycoplasma screening? Container closure integrity testing. Sterile filtration validations? Other tests? June 13, 2017 IVT Microbiology Week 43

44 Presentation Overview Rationale for outsourcing your microbiological testing Selection parameters Pre audit questionnaire Audit objectives Difference between a business contract and a quality agreement Important issues in building the relationship Method validation/suitability testing Failure investigations 483 observations Response to FDA Quality Metrics program June 13, 2017 IVT Microbiology Week 44

45 Failure Investigations Out of specification results will generate a laboratory investigation to determine if the sample was not compromised, the test was conducted correctly and the results are valid. This investigation will be conducted by the contract testing laboratory following a procedure approved by the client and will be fully documented. The client manufacturer would proceed with the manufacturing investigation, if the test was found to be valid. June 13, 2017 IVT Microbiology Week 45

46 Benchmarking Questions Is there adequate guidance available on microbiology failure investigations? What microbial test results are involved most frequently in laboratory investigations? How frequently does the investigation result in the invalidation of a test? Are drug products released after the invalidation of a test? June 13, 2017 IVT Microbiology Week 46

47 Simple Fishbone Diagram June 13, 2017 IVT Microbiology Week 47

48 June 13, 2017 IVT Microbiology Week 48

49 Failure Investigation The FDA Guidance for Industry, Investigating Out of Specification Test Results for Pharmaceutical Production states that contract testing labs should report their data, findings, and supporting documentation to the QC unit of the drug manufacturer, who should then, as necessary, initiate an OOS investigation. The guidance document describes the responsibility of the analyst and lab supervisor in conducting the lab investigation and emphasizes that lab error should be relatively rare, but when clear evidence of lab error exists, the results should be invalidated. June 13, 2017 IVT Microbiology Week 49

50 Laboratory Investigations In practice, the contract testing lab should know the test specification for the product being tested and immediately start a lab investigation using a procedure agreed upon by the contacting lab and your customer. OOS investigations and their outcomes should logged and trended. Importantly, the contract testing lab must trend invalidated OOS results as a measure of their analytical performance. The root cause of the invalidated result should be established and corrective action taken, i.e., CAPA. June 13, 2017 IVT Microbiology Week 50

51 Laboratory Investigations Whenever a laboratory error is identified, the source of the error would be determined and corrective action taken. Conversely, when no evidence of laboratory error is clear, the customer should conduct an investigation of their manufacturing operation, which is outside the scope of the contract testing laboratory. June 13, 2017 IVT Microbiology Week 51

52 Presentation Overview Rationale for outsourcing your microbiological testing Selection parameters Pre audit questionnaire Audit objectives Difference between a business contract and a quality agreement Important issues in building the relationship Method validation/suitability testing Failure investigations 483 observations Response to FDA Quality Metrics program June 13, 2017 IVT Microbiology Week 52

53 External Audits Contract testing laboratories are subject to external audits including: Customer audits for qualification or in response to test failures Audits from certification authorities FDA registration audits, recall follow ups and riskbased GMP inspections June 13, 2017 IVT Microbiology Week 53

54 FDA Warning Letter January 2012 warning letter to Biochem Laboratories Inc. Lyndhurst, NJ During our May 18, 2011 through June 15, 2011 inspection of your pharmaceutical contract testing laboratory, Biochem Laboratories Inc., located at 56 Park Avenue, Lyndhurst, New Jersey, investigators from the FDA identified significant violations of the CGMP regulations for Finished Pharmaceuticals, 21 CFR, Parts 210 and 211. These violations cause your clients' drug products to be adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. 351(a)(2)(B)] in that the methods used in, or the facilities or controls used for, their manufacture, processing, packing, or holding do not conform to, or are not operated or administered in conformity with, CGMP. June 13, 2017 IVT Microbiology Week 54

55 FDA Warning Letter January 2017 letter to Porton Biopharma, Limited, Porton Downs, UK: Firms acting as contract manufacturers must comply with cgmp. FDA is aware that many pharmaceutical product manufacturers use independent contractors, such as production facilities, testing laboratories, packagers, and labelers. FDA regards contractors as extensions of the manufacturer. You and your customer, Jazz Pharmaceuticals, have a quality agreement regarding the manufacture of Erwinaze. Regardless of this agreement, you are both responsible for the quality of drugs released and ultimately administered to patients. June 13, 2017 IVT Microbiology Week 55

56 MHRA Inspection Trends The 2015 UK Medicines and Healthcare Products Regulatory Agency GMP Inspections trends: There was no proceduralized assessment of the suitability of the Contract Acceptor There had been no documented assessment of the suitability of Contract Acceptor Technical Agreements and audits were not in place for a number of suppliers There was no inventory of Technical Agreements for outsourced activities and no review period Assessment of the competence of outsourced service providers was not always completed June 13, 2017 IVT Microbiology Week 56

57 Method Suitability Testing An FDA Warning Letter dated February 17, 2014 to a contract testing Biochem Laboratories, Inc, the Director of the New Jersey District wrote the following: In your response, you state that you have informed your clients on the importance of validating the methods, but they have chosen not to validate the methods. In addition, you state that you will inform them again in writing. Your response, however, is inadequate because you do not provide your firm s planned corrective actions for this cgmp violation. You are responsible for ensuring that the test methods used by your firm are validated. June 13, 2017 IVT Microbiology Week 57

58 Method Suitability Testing Your firm has failed to establish and document the accuracy, sensitivity, specificity, and reproducibility of test methods [21 CFR (e)]. Your firm failed to validate the specificity of the test procedures used to analyze finished product stability samples to ensure that the methods are stabilityindicating. For example, your firm determined the content of salicylic acid in (b)(4) stability samples by titration. Your firm has not demonstrated the specificity of the method for degradation products. June 13, 2017 IVT Microbiology Week 58

59 Presentation Overview Rationale for outsourcing your microbiological testing Selection parameters Pre audit questionnaire Audit objectives Difference between a business contract and a quality agreement Important issues in building the relationship Method validation/suitability testing Failure investigations 483 observations Response to FDA Quality Metrics program June 13, 2017 IVT Microbiology Week 59

60 Quality Metrics On July 28, 2015, FDA published Draft Guidance for Industry: Request for Quality Metrics in the Federal Register with a 60 day comment period. The intention of this long anticipated document is to establish a risk based frequency for the regulatory inspection program for pharmaceutical companies through review of quality metrics data on lot rejection rates, frequency of invalidated out ofspecification (OOS) results, product complaints, and on time rates for annual product and quality review reporting. June 13, 2017 IVT Microbiology Week 60

61 Benchmarking Questions Are you aware of the FDA program on Quality Metrics? Does your lab maintain quality metrics? Have FDA investigators requested information on the rate of invalidation of microbial tests? June 13, 2017 IVT Microbiology Week 61

62 Quality Metrics In 2016, the FDA released a draft Guidance for Industry, Request for Quality Metrics, which described the FDA s intent to require 10 types of quality data from the industry for both drug owners and their contractors, so that 4major quality metrics Lot Acceptance Rate, Product Quality Complaint Rate, Invalidated Out of Specification Rate and Annual Product Review on Time Rate can be calculated. The primary FDA use of the quality metrics is to develop risk based drug inspection schedules and address potential drug shortages See June 13, 2017 IVT Microbiology Week 62

63 FDA Intentions Quality metrics reporting would justify reduced general, pre approval, and post approval manufacturing change inspections and improve overall quality in the pharmaceutical industry. Taking up the theme introduced by Jill Wechsler in her July 29, 2015 Regulatory Beat column, the carrots for the pharmaceutical industry are the promise of a reduced frequency of regulatory inspections, whereas the stick if quality metrics are not reported is the possibility of having products designated as adulterate in terms of the Federal Food, Drug, and Cosmetic Act (FD&C Act). June 13, 2017 IVT Microbiology Week 63

64 Affect on Contract Testing Labs Are contract testing laboratories conducting release and stability testing for drug manufacturers required to maintain and report quality metrics? The short answer is, probably no. Of the seven major quality metrics FDA plans to monitor number of lots attempted, number of lots rejected, number of tests conducted, number of OOS results, number of invalidated OOS results, number of lots released, and number of product complaints for each drug product only the quality metrics related to OOS results directly impact contract testing labs. June 13, 2017 IVT Microbiology Week 64

65 Lab Investigations The FDA Guidance for Industry, Investigating Out of Specification Test Results for Pharmaceutical Production states that contract testing labs should report their data, findings, and supporting documentation to the QC unit of the drug manufacturer, who should then, as necessary, initiate an OOS investigation. The guidance document describes the responsibility of the analyst and lab supervisor in conducting the lab investigation and emphasizes that lab error should be relatively rare, but when clear evidence of lab error exists, the results should be invalidated June 13, 2017 IVT Microbiology Week 65

66 Quality Metrics In practice, a contract testing lab should know the test specification for the product being tested and immediately start a lab investigation using a procedure agreed upon by the contacting lab and your customer. OOS investigations and their outcomes should logged and trended. Importantly, the contract testing lab must trend invalidated OOS results as a measure of their analytical performance. The root cause of the invalidated result should be established and corrective action taken. June 13, 2017 IVT Microbiology Week 66

67 Quality Metrics How will these regulatory changes impact contract testing laboratories? With OOS results being a key quality metric, more attention must be given to this crucial area. As an observer of the state of contract testing, I see many challenges resulting from these upcoming regulatory changes. June 13, 2017 IVT Microbiology Week 67

68 Quality Metrics Samples may be submitted by pharmaceutical companies to contract testing laboratories via purchase orders with one or more of the following issues: No identification as to dosage form and product name; Test procedures requested that are not fully described Sample size may not comply with compendial test requirements Testing laboratories may not be fully aware of product specifications Test methods may not be adequately qualified. June 13, 2017 IVT Microbiology Week 68

69 Quality Metrics These potential issues all make it difficult for the contract laboratory to test, evaluate, and identify an OOS result. Although a manufacturer may reject a lot based on the reported results from the contract laboratory, this does not negate the need to perform an OOS investigation. In a few isolated cases, misguided manufacturers may resubmit additional samples from the same batch for testing without the knowledge of the contract laboratory in an attempt to test the product into compliance with the specification. June 13, 2017 IVT Microbiology Week 69

70 Quality Metrics Because many manufacturers are increasingly outsourcing release and stability testing as a costsavings strategy, they may be tempted to skimp on ordering OOS investigations. The requirements for annually reporting lots attempted, OOS results, OOS results invalidated, and lots rejected will open a manufacturer up to additional regulatory scrutiny. June 13, 2017 IVT Microbiology Week 70

71 Conclusions As microbiologists we should be involved in any decisions to outsource microbiological testing Get involved to take care of the interests of your staff and the reputation of your company. Thank for your attention. Are there any additional questions or comments? June 13, 2017 IVT Microbiology Week 71