Re: Docket No. FDA-2009-D-0179, Technical Considerations for Pen, Jet, and Related Injectors Intended for Use with Drugs and Biological Products
The Biotechnology Industry Organization (BIO) thanks the Food and Drug Administration (FDA) for the opportunity to submit comments on the Draft Guidance for Industry and FDA Staff: Technical Considerations for Pen, Jet, and Related Injectors Intended for Use with Drugs and Biological Products.
BIO represents more than 1,200 biotechnology companies, academic institutions, state biotechnology centers and related organizations across the United States and in more than 30 other nations. BIO members are involved in the research and development of innovative healthcare, agricultural, industrial and environmental biotechnology products, thereby expanding the boundaries of science to benefit humanity by providing better healthcare, enhanced agriculture, and a cleaner and safer environment.
BIO agrees with FDA‟s assessment that “pen, jet, and related injectors may provide an innovative approach to deliver drugs or biological products and may enhance safety, improve dosing accuracy, and increase patient compliance, particularly in self administration settings.” (Lines 56-58) Indeed, the innovation of the biotechnology industry extends into drug delivery, and novel injector approaches are improving the convenience of administering drugs, minimizing pain and suffering, and maximizing medical outcomes for patients. Injector technologies are rapidly evolving as pre-filled pens, jet, and needleless technologies become more common. However, these advancements also pose the question of what regulatory submissions should be provided to FDA to assure the safety and reliability of new injector systems. BIO applauds FDA for releasing this draft guidance to industry and seeking to establish the least burdensome approach for regulatory submissions regarding pen, jet, and related injectors. We are pleased to offer the following general and technical comments in support of the guidance.
Our comments primarily fall under three general areas which address concerns that the guidance as currently drafted: (1) does not represent a least burdensome approach; (2) does not address application of Risk Management and or Quality System requirements in determining the need for scientific and technical information to support device submissions; and (3) does not address how the issuance of this guidance will impact current products in the market. Under our general comments we list specific comments that support our general concerns where appropriate.
I. Not Representative of the Least Burdensome Approach:
This guidance does not achieve the least burdensome approach in addressing technical and scientific development considerations for injectors particularly in the areas of: (1) data requirements, (2) product classification, and (3) labeling requirements.
1. Data Requirements: The guidance addresses a broad spectrum of devices (e.g., devices that are mechanical vs. devices that are electromechanical, devices that are general use vs. devices/combination products that are specific use) and provides recommendations for the scientific and technical data needed to support marketing applications covering all of them without distinction between the complexity of the different devices or their intended use. As a result the guidance fails to provide a least burdensome approach in particular for general use injectors and New Drug Applications (NDA) or Biologic License Applications (BLA) in which an injector is already approved.
Rather than providing a list of requirements covering all devices, regardless of complexity or intended use, the guidance should address the requirements for specific classes of devices having comparable features. We recommend that the agency consider including a table or a series of tables that specify data expectations for common injector categories (A proposed table format can be found in the appendix to these comments). Under this approach, the table could list the specific submission and testing expectations for a base case for a typical injector configuration and then provide additional considerations for the more complex scenarios.
Specific examples in the guidance of overly burdensome data requirements can be found in the specific comments section addressing: line 165-185; line 181-185; line 239; line 282-294; line 298-366; line 476-479; line 628-629; line 632-636; line 634-636.
2. Existing FDA Guidance on Submission Requirements and Product Classification Codes for Piston Syringes and Pens: Submission requirements for piston syringes and pen injectors are covered in an existing FDA guidance document, Guidance on the Content of
Premarket Notification Submissions for Piston Syringes. Pen injectors fall under very broad product classification codes so applicability of guidance for these devices in the existing FDA guidance and the proposed draft guidance could force manufacturers to comply with two separate and at times conflicting guidance documents. This certainly would not qualify as a least burdensome approach. We recommend that FDA clarify expectations regarding applicability of guidance to specific classes of devices covered by the different guidance documents or state whether the new guidance document will replace the existing guidance document which covers piston syringes and pens.
3. Labeling Requirements: The draft Injector guidance provides overly burdensome requirements for labeling. Instead of including specific requirements for labeling in the guidance, it would be more appropriate to reference the labeling requirements of 21 CFR Part 801 and existing Center for Devices and Radiological Health (CDRH) guidances for patient labeling.
Specific examples in the guidance of overly burdensome labeling requirements can be found in the specific comments section addressing: line 296-333; Section I.H Labeling: line 830-865.
II. Application of Risk Management and or Quality System Requirements in Determining the Need for Scientific and Technical Information to Support Device Submissions:
BIO requests that the guidance discuss the application of Quality Systems, use of risk assessments in device development, or specific requirements associated with self-administration/home use of a product.
The application of quality systems is a key issue that is not addressed within the guidance document. The confusion around the application of quality systems is a well known issue with combination products. We recommend that the agency provide direction on how to balance the differences between Part 820 and Parts 211/600, especially for topics like Design Controls and Purchasing Controls, as these topics are very relevant to the development of the type of products covered by this guidance and help guide technical requirements and documentation. For example, the guidance document refers to design verification and validation activities that would generally take place as part of design controls for a medical device, but does not mention the necessity for documenting the design inputs that define what is tested through design verification and validation. In addition the guidance does not address planning for this testing as would be done in a Design and Development Plan, nor does it address where this data should be kept, for example in a Design History File. Another critical area to address in the guidance document would be Purchasing Controls. With combination products there is often a device company working with a pharmaceutical company, and there is a need to clarify expectations for setting specifications for purchased materials and provide direction on acceptance procedures and sampling for incoming inspection.
Another area that is inadequately addressed is the application of risk management in device development. This should be clearly identified as a decision making tool for manufacturers, to determine the requirements they will need to meet based on the level of risk associated with use of a device in patients. The guidance would be less burdensome if the recommend requirements were triaged by risk. Further, it would be helpful if the guidance document provided some insight on how to balance the application of the device Risk Management standard (ISO 14971:2007) and the drug Risk Management standard (ICH Q9). As currently drafted it appears as if every device, regardless of risk or complexity, would be expected to follow each recommendation in the guidance.
Specific examples in the guidance of how application of risk assessment could be used in making decisions regarding the data recommendations for specific injection devices can be found in the specific comments section addressing: line 408-415; line 439; line 584-585; line 625; line 653-655; line 713-720.
III. Legacy Products and Post Approval Changes:
This guidance addresses the technical and scientific information needed to support a marketing application for a pen, jet, or related injector device intended for use with drugs and biological products, but does not address the reporting requirements and data needed to support post approval changes to an already approved injector device used with a drug or biological product. Post approval changes to an injector submitted for approval in the drug or biological product license would typically be reported in a supplement to the NDA or BLA. However, guidance as to the applicability of suggested reporting requirements under drug/biologic or device regulations for changes to the injector is not provided. We recommend that FDA clarify that legacy products and future supplements for those products are outside of the scope of this guidance. In addition, clarity is needed on the applicability of the recommendations in this guidance to already approved injector/pen products or relevant combination products already in the market place.
BIO appreciates this opportunity to comment on Technical Considerations for Pen, Jet, and Related Injectors Intended for Use with Drugs and Biological Products. We have provided specific comments in Appendix 1 and a proposed table format for describing data requirements for specific injector classes in Appendix 2. We would be pleased to provide further input or clarification of our comments, as needed.
Andrew J. Emmett
Director for Science and Regulatory Affairs
Biotechnology Industry Organization (BIO)