Test and Control Article Characterization for Medical Devices. Amy Schade, RQAP-GLP Director Corporate Compliance

Transcription

1 for Amy Schade, RQAP-GLP Director Corporate Compliance

2 Disclaimer» This presentation is not intended to encompass all of the requirements of the FDA, EPA, OECD or other regulatory programs for all types of products or materials.» The content represents the viewpoints and opinion of the speaker and not SQA or their employees.» Perceptions and experiences of a Contract Research Laboratory

3 FDA 21 CFR part 58 Good Laboratory Practice» Test and control article characterization» (a) The identity, strength, purity, and composition or other characteristics which will appropriately define the test or control article shall be determined for each batch and shall be documented. Methods of synthesis, fabrication, or derivation of the test and control articles shall be documented by the sponsor or the testing facility.» In those cases where marketed products are used as control articles, such products will be characterized by their labeling.

4 » (b) The stability of each test or control article shall be determined by the testing facility or by the sponsor either: (1) Before study initiation, or (2) concomitantly according to written standard operating procedures, which provide for periodic analysis of each batch.

5 » (c) Each storage container for a test or control article shall be labeled by name, chemical abstract number or code number, batch number, expiration date, if any, and, where appropriate, storage conditions necessary to maintain the identity, strength, purity, and composition of the test or control article.» Storage containers shall be assigned to a particular test article for the duration of the study.

6 » (d) For studies of more than 4 weeks' duration, reserve samples from each batch of test and control articles shall be retained for the period of time provided by [43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33781, Sept. 4, 1987; 67 FR 9585, Mar. 4, 2002]

7 » Test and Control Article Characterization Identity Strength Purity Composition Other characteristics Method of synthesis, fabrication, or derivation Stability Labeling : Name, CAS, code, batch, lot, expiration date Retention» What is being tested and how are you going to prove it?

8 Drugs Trade name on the front with NDC# Active ingredients Lot # & Exp Date on Side of box Inactive ingredients Instructions for Use

9 Typical medical devices submitted for testing Photos from Google Images

10 Devices N/A Label from Google Images Provided on package insert

11 Options for Characterizing a Medical Device Identity: Name of the device/component, catalog number, part number, lot/batch number Describe its intended use Strength: Generally N/A, combination devices would add drug info Purity: Generally N/A, combination device would add drug info Composition: Identify the types of materials such as plastics, metals, inks, components Method of synthesis, fabrication, or derivation: How was the device made (molded vs extruded), cross reference Design Master file traceability number. Stability: Details regarding stability of the materials and components/shelf life Labeling: CAS, code, product number, batch, lot, expiration date, sterility, non-pyrogenic, not for human use Other characteristics: Color, length, size, volume, software & version, final clinical design or not, sterilization method, accessories, instructions for use, method of sterilization

12 Critical characterization information that is often missing: A description of the intended use If Test Facility Management and the Study Director are unaware of the intended use, testing programs may not be correctly designed to assure the safety of the test article. Technical references for the execution of the testing methods are often viewed as one-size-fits-all. However, there are nuances for specific types of drugs or device materials that have to be considered in study designs to assure the a test article is appropriately challenged.

13 Who is responsible? 21 CFR part Testing facility management (d) Assure that the test and control articles or mixtures have been appropriately tested for identity, strength, purity, stability, and uniformity, as applicable. The study director is unable to draw conclusions if the characterization data is unavailable.

14 At a CRO, how is this assurance accomplished by management? (e) Assure that personnel, resources, facilities, equipment, materials and methodologies are available as scheduled. Standard Operating Procedures Effectively applied Sales (educate Sponsors) Study Directors (control of the study) QA Inspections (inspect for content)

15 The big question! GMP vs GLP Characterization?

16 » At a very simplistic level: GMPs apply to finished devices/drug GLPs apply to nonclinical testing How does a Sponsor, who operates a GMP facility, perform characterization testing GLP? Test Facility Management? Study Director? QAU? SOPs? Protocols, data collection, reporting, archiving? Or Subcontract it

17 » FDA Q&A Document 1981(original), 1999 (edits), 2007 (edits) Q: Are physical and chemical tests conducted on test articles required to be done under the GLPs? A: According to section , such tests conducted to characterize the specific batch for test article use in the nonclinical study are covered Q: What constitutes proper QA Unit inspection of each phase of a nonclinical laboratory study? A: The phases of a particular study will be determined by the nature of the study. For example Test article characterization Test article stability Test article-carrier mixture homogeneity determination

18 » FDA Q&A Document 1981(original),1999 (edits), 2007 (edits) Q: Am I correct in assuming that the chemical testing done by the sponsor to characterize the test article is covered by the GLPs when the test article is subsequently submitted to a contract laboratory as a blind sample for safety testing A: The GLPs do not cover basic exploratory chemical testing done to derive the specifications of the test article. They do cover those chemical tests done on discrete batches of test article to determine identity, strength, purity and composition. According to section , such tests conducted to characterize the specific batch for test article use in the nonclinical study are covered

19 FDA Compliance Program Guidance Manual» Bioresearch Monitoring for GLPs Establishment Inspection The facility inspection should be guided by the GLP regulations. The following areas should be evaluated and described as appropriate. Determine if management assured that test and control articles or mixtures are appropriately tested for identity, strength, purity, stability, and uniformity. Test and Control Articles» In bold and underlined! When test article characterization and stability testing is performed by the sponsor, verify that the test facility has received documentation that this testing has been conducted

20 » What if the characterization testing was not done GLP? Report as a GLP exemption in the final report Describe what steps were taken to assure the validity and integrity of the data which supports the characterization. A simple statement indicating that something was prepared GMP-like is not sufficient.

21 » Retention samples For studies of more than 4 weeks' duration, reserve samples from each batch of test and control articles shall be retained for the period of time provided by Who is responsible for retention? The FDA GLPs do not assign responsibility for this (Sponsor vs CRO), however protection of the material from deterioration and contamination is required for as long as the material affords evaluation.

22 Thank you! Amy Schade, RQAP-GLP Director Corporate Compliance Toxikon Corporation