GMP, GLP OR ISO 17025: HOW DO THESE APPLY TO OUTSOURCED ANALYTICAL TESTING?

Transcription

1 GMP, GLP OR ISO 17025: HOW DO THESE APPLY TO OUTSOURCED ANALYTICAL TESTING? Joe Grappin, MS, EAG Laboratories 2018 MD&M West Tech Theater 1

2 OVERVIEW Background: What Led to the Presentation History of the Regulations When and where the GLP s apply to Medical Device Testing? What is GMP testing and how does it apply to Medical Device Testing? What does ISO mean? Decision Tree Summary Questions 2

3 BACKGROUND: WHAT LED TO THE PRESENTATION My experience: Ten years of experience managing pharmaceutical container-closure testing in an analytical laboratory Seven years of experience managing and directing a medical device analytical testing laboratory Seven years of experience on the front line, selling laboratory testing capabilities to medical device clients What led to the Presentation? Clients frequently requested some answers to the following questions 3

4 CLIENT QUESTIONS Are you a GLP lab? Are you a GMP lab? Are you registered by the FDA? What type of quality system do you have in place? Are your instruments validated? What certifications do you have? Are you ISO certified? What is ISO 17025? 4

5 HISTORY OF THE REGULATIONS Good Laboratory Practices (GLP): Series of unfortunate events in 1960 s and 1970 s at pre-clinical (animal) laboratories Poor record-keeping Poorly designed studies Lack of oversite Animal resurrections 5

6 HISTORY OF THE REGULATIONS Determination by members of congress and the FDA that these laboratories were out of control. December 1978: FDA published final GLP regulations June 1979: Title 21 Food and Drugs of the Code of Federal Regulations (CFR) as Part 58. Good Laboratory Practice for Nonclinical Laboratory Studies Further changes to the GLP rules in 1984 and 1987: "Final Rule" - Compliance Program Bioresearch Monitoring: Good Laboratory Practices, which was expanded to incorporate the following: The requirement for a QA department The requirement for protocol preparation (study plan) The characterization of test and control materials The requirement to retain specimens and samples. 6

7 HISTORY OF THE REGULATIONS Good Manufacturing Practices (GMP) Developed in response to a series of problems involving the quality and safety of pharmaceuticals (drugs) 1930 s: Elixir of Sulfanilamide and sulfathiazole 1950 s and 1960 s: Polio vaccine and thalidomide The drug GMPs were established in 1963, expanded in 1978 and revised slightly in CFR Part 210: CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, PROCESSING, PACKING, OR HOLDING OF DRUGS; GENERAL 21 CFR Part 211: CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS 7

8 HISTORY OF THE REGULATIONS In 1978, when the Drug GMP s were expanded it was determined that Medical Device needed their own GMP s. Medical device manufacturing has a wide variety of processes when compared to pharmaceutical manufacturing Pharmaceutical products have biological activity where potency is critical. 21 CFR Part 820 Medical Devices, Quality System Regulations Revised in 1996 Harmonized with ISO 13485: Medical devices Quality management systems Requirements for regulatory purposes 8

9 HISTORY OF THE REGULATIONS Similarities and Differences between the Drug and Device GMP s Both are written describing general quality system requirements such as requiring the use of calibrated instruments for measurements. Drug GMP s go further in defining laboratory testing: 21CFR (b): Laboratory controls shall include the establishment of scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity. 9

10 HISTORY OF THE REGULATIONS 21CFR (b): Laboratory controls shall include: Description of sampling plan, testing procedure and specifications Determination of conformance to specifications of in-process and drug products Calibration of instruments with limits of accuracy and precision defined 10

11 WHEN AND WHERE THE GLP S APPLY TO MEDICAL DEVICE TESTING Why wouldn t you want a lab to perform your test or study using good laboratory practices? The key is understanding why the GLP s were put in place to begin with: Control (or lack there of) in the pre-clinical laboratory Complex test systems, such as animal models or cell lines Observation-based 11

12 WHEN AND WHERE THE GLP S APPLY TO MEDICAL DEVICE TESTING Regulations define the scope of the GLP s Nonclinical laboratory study means in vivo or in vitro experiments in which test articles are studied prospectively in test systems under laboratory conditions to determine their safety. The term does not include studies utilizing human subjects or clinical studies or field trials in animals. The term does not include basic exploratory studies carried out to determine whether a test article has any potential utility or to determine physical or chemical characteristics of a test article. 12

13 WHEN AND WHERE THE GLP S APPLY TO MEDICAL DEVICE TESTING Questions to ask: 1. Is the study that I want to be performed use a test system as defined in 21 CFR part 58 (Animal model or cell line)? 2. Is the study considered exploratory and early stage investigational? Is the study not planning to be used in a submission? Prior to design freeze? 3. What if the study supports a corresponding GLP study? 4. Are there such things as non-glp studies? 13

14 WHEN AND WHERE THE GMP S APPLY TO MEDICAL DEVICE TESTING So your study does not fall under the GLP requirements Can I ask to have it done under GMP requirements? Answer: It depends Where is your study supporting in the Medical Device development process? 14

15 WHEN AND WHERE THE GMP APPLY TO MEDICAL DEVICE TESTING Questions to ask: 1. Is the study in support of an in-process inspection of a device or material? 21CFR Is the study in support of a process verification? 21CFR Is the material being tested the active pharmaceutical ingredient, excipient or container closure/delivery system of the drug-device combination product? 21CFR 210/ What if none of these scenarios apply? 15

16 WHEN AND WHERE THE GMP S APPLY TO MEDICAL DEVICE TESTING Is there enough direction in 21 CFR part 820 for the laboratory testing? 21CFR : Inspection, Measuring, and Test Equipment Control of inspection, measuring, and test equipment. Calibration Calibration standards Calibration records Applies to the manufacturing site and does not call out the details of what is acceptable. Is there another mechanism to ensure that my outsourced laboratory is producing results with a high level of scientific quality and would meet regulatory expectations? 17

17 WHAT IS ISO AND HOW DOES IT APPLY TO THE MEDICAL DEVICE INDUSTRY ISO General Requirements for the Competence of Testing and Calibration Laboratories. Main ISO standard used by testing and calibration laboratories. In most major countries, ISO/IEC is the standard for which most labs must hold accreditation in order to be deemed technically competent. The standard requires the use of certified calibration materials Trending of instrument data Competency of analysts Technique evaluated for the uncertainty of the measurements 18

18 WHAT IS ISO AND HOW DOES IT APPLY TO THE MEDICAL DEVICE INDUSTRY ISO General Requirements for the Competence of Testing and Calibration Laboratories. (Continued) Aligns with ISO and 21 CFR 820 in terms of quality management and documentation. Complements 21CFR part 58, not required Written specifically for laboratory operations If only performing GMP testing per 21 CFR 210/211, then ISO is not needed. Will FDA accept submission data from a ISO laboratory? ABSOLUTELY! 19

19 DECISION TREE 20

20 SUMMARY Not one set of regulations that covers every medical device testing situation. Applying the wrong regulation or standard could be detrimental to the overall time to market. The laboratory needs to provide scientific solutions that can meet the regulatory scrutiny of the industry. 21

21 QUESTIONS 22

22 THANK YOU Contact information: Joe Grappin EAG Laboratories 810 Kifer Road Sunnyvale, CA Phone:

23 THE POWER OF SCIENCE TO SHAPE COMMERCE How do you make a product better, easier to use or less expensive? How do you ensure regulatory compliance or strengthen your legal case? How do you bring powerful scientific know-how across materials sciences, engineering sciences and life sciences to your commercial challenges? Ask EAG. We Know How.