via flickr by joel mark witt
I’m writing this post in response to a computer systems validation I performed. The client I was working with utilized human tissues to create their tissue-based product. During the validation, the client ask me what regulations required them to validate their computer system. The answer is found in the link to the FDA’s website for 21 CFR Part 1271. In particular, within Subpart D: Current Good Tissue Practices requires computer system validation under, 1271.160 (d) Computers. To understand which companies are governed by this requirement is a bit tricky to follow at first but easy to understand after reading my blog. This post is relevant to companies that deal with human cell, tissues, and cellular and tissue based products within their process or as part of their product (HCT/P’s).
First Step: Understanding Subpart A: General Provisions 1271.1 (b) Scope
This section of the regulation defines which establishments that manufacture human cells, tissues, and cellular and tissue-based products (HCT/P’s) fall into either of two categories: solely regulated under section 361 of Public Health Services (PHS) Act (see section 1271.10) or those HCT/P’s that are regulated as drugs, devices and/or biological products under section 351 of PHS Act and/or the Federal Food, Drug, and Cosmetic Act, Secs. 210.1(c), 210.2, 211.1(b), and 820.1(a) will require compliance with current good tissue practices under Subpart D.
If you are within the former group, further determination must be done to see if you are governed by Subpart D,current good tissue practices, by examining section 1271.10.
If you are in the later, Subpart D already applies. Later on, I will address computer validation requirements.
If you don’t meet the requirements of 1271.10 and don’t fall under the exceptions of 1271.15, you fall under the scope of these requirements including Subpart D.
Subpart A: Section 1271.10
I copies this link directly from the FDA hyperlink above. Basically, if you meet the requirements of this section, only Subpart A of 1271 applies.
Sec. 1271.10 Are my HCT/P’s regulated solely under section 361 of the PHS Act and the regulations in this part, and if so what must I do?
(a) An HCT/P is regulated solely under section 361 of the PHS Act and the regulations in this part if it meets all of the following criteria:
(1) The HCT/P is minimally manipulated;
(2) The HCT/P is intended for homologous use only, as reflected by the labeling, advertising, or other indications of the manufacturer’s objective intent;
(3) The manufacture of the HCT/P does not involve the combination of the cells or tissues with another article, except for water, crystalloids, or a sterilizing, preserving, or storage agent, provided that the addition of water, crystalloids, or the sterilizing, preserving, or storage agent does not raise new clinical safety concerns with respect to the HCT/P; and
(i) The HCT/P does not have a systemic effect and is not dependent upon the metabolic activity of living cells for its primary function; or
(ii) The HCT/P has a systemic effect or is dependent upon the metabolic activity of living cells for its primary function, and:
(a ) Is for autologous use;
(b ) Is for allogeneic use in a first-degree or second-degree blood relative; or
(c ) Is for reproductive use.
(b) If you are a domestic or foreign establishment that manufactures an HCT/P described in paragraph (a) of this section:
(1) You must register with FDA;
(2) You must submit to FDA a list of each HCT/P manufactured; and
(3) You must comply with the other requirements contained in this part.
Subpart A: Section 1251.15 -Exceptions
If you meet the criteria below, you fall under exceptions and do not need to meet the criteria in Subpart A. Again, this is directly from the FDA hyperlink above.
Sec. 1271.15 Are there any exceptions from the requirements of this part?
(a) You are not required to comply with the requirements of this part if you are an establishment that uses HCT/P’s solely for nonclinical scientific or educational purposes.
(b) You are not required to comply with the requirements of this part if you are an establishment that removes HCT/P’s from an individual and implants such HCT/P’s into the same individual during the same surgical procedure.
(c) You are not required to comply with the requirements of this part if you are a carrier who accepts, receives, carries, or delivers HCT/P’s in the usual course of business as a carrier.
(d) You are not required to comply with the requirements of this part if you are an establishment that does not recover, screen, test, process, label, package, or distribute, but only receives or stores HCT/P’s solely for implantation, transplantation, infusion, or transfer within your facility.
(e) You are not required to comply with the requirements of this part if you are an establishment that only recovers reproductive cells or tissue and immediately transfers them into a sexually intimate partner of the cell or tissue donor.
(f) You are not required to register or list your HCT/P’s independently, but you must comply with all other applicable requirements in this part, if you are an individual under contract, agreement, or other arrangement with a registered establishment and engaged solely in recovering cells or tissues and sending the recovered cells or tissues to the registered establishment.
Subpart A: Section 1271.20
So if you don’t meet the criteria in Section 1271.10 and don’t fall under the exceptions of 1271.15, you are governed by all requirements listed below and Subpart D. Therefore, you need to follow the computer system validation guidelines which falls under Subpart D, 1271.160-Establishment and maintenance of a quality program.
Sec. 1271.20 If my HCT/P’s do not meet the criteria in 1271.10, and I do not qualify for any of the exceptions in 1271.15, what regulations apply?
If you are an establishment that manufactures an HCT/P that does not meet the criteria set out in 1271.10(a), and you do not qualify for any of the exceptions in 1271.15, your HCT/P will be regulated as a drug, device, and/or biological product under the act and/or section 351 of the PHS Act, and applicable regulations in title 21, chapter I. Applicable regulations include, but are not limited to, 207.20(f), 210.1(c), 210.2, 211.1(b), 807.20(d), and 820.1(a) of this chapter, which require you to follow the procedures in subparts B, C, and D of this part.
Subpart D: Section 1271.160 Establishment and maintenance of a quality program (d) Computers.
This is the actual requirement found within 1271 that directly addresses the need to validate computer software. I copied only section (d) from the page.
(d)Computers . You must validate the performance of computer software for the intended use, and the performance of any changes to that software for the intended use, if you rely upon the software to comply with core CGTP requirements and if the software either is custom software or is commercially available software that has been customized or programmed (including software programmed to perform a user defined calculation or table) to perform a function related to core CGTP requirements. You must verify the performance of all other software for the intended use if you rely upon it to comply with core CGTP requirements. You must approve and document these activities and results before implementation.
Note the following from above as it relates to software utilized to meet CGTP in its intended use:
Validation is required for software in its intended use.
Validation is required of any changes to the software for its intended use.
Customized, commercially available both require the same validation.
User defined calculation or table actions apply.
All software you rely upon for core CGTP requirements fall under this category.
You must APPROVE and DOCUMENT these activities and results before implementation.
The FDA database was updated April 1, 2008 according to the FDA website. Check the FDA Website often to confirm the most current version of the regulations are available.
Additional Guidance for Computer Systems and Validation Activities
There are many software providers and consultants that assist companies with meeting the requirements of 1271. It is important to make a good selection after an informed decision. I recommend reviewing the FDA Guidance Document on the subject of Computer System Validation as well as GAMP5 guidelines, among others. Make sure that any software vendor or validation consultant has a good understanding of your process, quality system requirements, and is willing to meet your internal standards. Always consult with professional QA/RA personnel before making any quality/regulatory decisions.
I welcome any and all feedback on my posts.
If you are interested in how my expertise can contribute to your validation project or company, please contact me at greggsalomon @ yahoo dot com.