Plamena Entcheva-Dimitrov, PhD, RAC On-line Course.

Transcription

1 Plamena Entcheva-Dimitrov, PhD, RAC On-line Course 1

2 The Preferred Regulatory Consulting content in this presentation is copyright protected under United States law and applicable international copyright laws. 2

3 Definition A product comprised of two or more regulated components, i.e., drug/device, biologic/device, drug/biologic, or drug/device/biologic, that are physically, chemically, or otherwise combined or mixed and produced as a single entity Two or more separate products packaged together in a single package or as a unit and comprised of drug and device products, device and biological products, or biological and drug products A drug, device, or biological product packaged separately that according to its investigational plan or proposed labeling is intended for use only with an approved individually specified drug, device, or biological product where both are required to achieve the intended use, indication, or effect and where upon approval of the proposed product the labeling of the approved product would need to be changed, e.g., to reflect a change in intended use, dosage form, strength, route of administration, or significant change in dose Any investigational drug, device, or biological product packaged separately that according to its proposed labeling is for use only with another individually specified investigational drug, device, or biological product where both are required to achieve the intended use, indication, or effect Examples Drug Eluting Stents; Drug Coated Balloons; Drug Coated Leads; Human-based collagen mixed with 0.3% lidocaine; condom coated with spermicide Inhalers packaged with drugs, but not prefilled; surgical tray containing lidocine or alcohol swabs Investigational product to be crosslabeled after approval for use with a commercial product; the commercial product will need to be cross-labeled, too; Photosensitizing drug and its activating laser/light source Two investigational products, which will be cross-labeled after obtaining approval; Iontophoretic drug delivery patch and the controller 3

4 Office of Combination Products (OCP) Intercenter agreements Established with MDUFMA in 2002 Central location to resolve jurisdiction issues Brings consistency in the decision process Coordination role Develops guidances Reports to congress yearly Request for Designation (RFD) 21 CFR 3.7 This is a submission to the OCP Very stringent format and content requirements FDA Guidance - How to Write a Request for Designation (RFD), April 2011 FDA issues the designation within 60 days Mechanism to request reconsideration of the FDA decision 4

5 Primary Mode of Action (PMOA) Primary mode of action is the single mode of action of a combination product that provides the most important therapeutic action of the combination product. i.e. Which of the components is doing the job? The most important therapeutic action is the mode of action expected to make the greatest contribution to the overall intended therapeutic effects of the combination product Determines the jurisdiction - Consult inter-center agreements CDRH: the device is doing the job, e.g. drug eluting stent CDER: the drug is doing the job, e.g. drug eluting transdermal patch CBER: stem cells delivered via catheter 5

6 Drug Eluting Stents (CDRH) Birth control patch (CDER) Neupro Patch for Treatment of Early Parkinson's Disease (CDER) Recombinant human bone graft (CDRH) Absorbable Hemostatic Agent (CDRH) Human-Based Collagen Implants (CDRH) Intravascular catheter packaged and labeled for delivering stem cells to treat myocardial infarction (CBER) Vaginal drug-delivery rings (CDER) 6

7 21 CFR Part 4: issued in Jan 2013, effective in July 2013 Constituent parts of a combination product retain their regulatory status (e.g. as a drug or device) after they are combined The cgmp requirements that apply to each of the constituent parts continue to apply when they are combined to make combination products All companies that manufacture combination products must comply with 21 CFR Part 4 The traditional drug companies must implement 21 CFR 820 principles The traditional medical device companies must implement 21 CFR 210 and 211 principles FDA is working on a DRAFT guidance on cgmps for combination products AAMI is working on a Technical Information Report to help manufacturers implement Part 4 7

8 In the case of device companies that are already compliant to 21 CFR 820, the following drug regulations need to be followed: Section (21 CFR Part 211) Element Testing and Approval r Rejection of Components, drug product containers and closures Calculation of Yield Tamper-evident Packaging for OTC Expiration Dating/Storage Conditions Testing and Release for Distribition Stability Testing Special Testing Requirements Reserve samples 8

9 Drug Guidelines such as ICH guidelines are applicable for combination products, such as: Stability Q1A to Q1F Analytical Validation Q2 Impurities Q3A to Q3D Specifications Q6a to Q6B GMP Q7 Etc 9

10 In the case of drug companies that are already compliant to 21 CFR 20/211, the following device regulations need to be followed: Section (21 CFR Part 820) Element Management Responsibility Design Controls Purchasing Controls CAPA Installation Servicing 10

11 Device Guidelines and Standards such as ISO standards are applicable for combination products, such as: ISO Aseptic processing of health care products -- Part 7: Alternative processes for medical devices and combination products ISO/TS Cardiovascular implants and extracorporeal systems -- Vascular device-drug combination products Guidance for Industry and FDA Staff: Technical Considerations for Pen, Jet, and Related Injectors Intended for Use with Drugs and Biological Products 11

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