English Requirement for FDA GMP Documents
Generally, overseas manufacturers in non-English speaking countries have their GMP documentation in the local language so that the staff working at the facility are able to read and understand the material. The choice of whether to use English or the native language is determined by the company and there is no requirement by the U.S. FDA to have all GMP documents at the site available in English for an inspection. The most important factor to consider when choosing whether to have your GMP documentation in English or the native language is to use a common format that is easily understandable to the staff working at the company for their particular operations. GMP documents in non-English format may include SOPs, investigations, internal communications and all other GMP related documentation.
For U.S. FDA international pharmaceutical inspections; it is common to see GMP documentation in the local native language of the country.
The most important aspect to consider is that regardless of the chosen language; the content of the GMP documentation has to be thorough and complete. Audits by vendors and U.S. FDA may be more difficult for the site to perform because reliance on a translator will be required throughout the inspection to translate documentation and also translate discussions with staff at the facility. During the inspection, the company is required to provide documents and information for review in a format that is understood by the U.S. FDA regulator which is typically English unless the auditor or regulator is fluent in the local native language. Conducting audits and inspections in a non-English country can be challenging as well as time consuming for the auditor and regulator. When conducting inspections in non-English speaking countries, there is a tendency for the auditor and regulator to spend additional time conducting walk-throughs of the facility and interviewing staff conducting operations on the floor rather than spending a majority of the time reviewing documentation in a conference room due to the additional time it takes to translate documents.
Audits and regulatory inspections in non-English speaking countries typically involve a translator sitting at the table and verbally translating and explaining a document along with a subject matter expert. When requested during the inspection, the site should also provide written translation of documents for the U.S. FDA regulator to collect for evidence gathering activities. However, translation of documents from the local language to English is typically a very time-consuming process and the regulator generally only requires very limited sections of documents or procedures translated for evidence gathering activities because of the time constraint. During the audit or inspection, it is important to get clarifications on the exact request for any written translations to avoid any confusion and unnecessary time delays. It is also important for the company to explain the approximate amount of time that it will take to provide the translation. The U.S. FDA regulator should be collecting and submitting documents collected from the site in English as evidence for the Establishment Inspection Report according to the Investigation Operation Manual (IOM) 2019 Chapter 1 and 5. The IOM is the U.S. FDA Standard Operating Procedure for conducting inspections, investigations, sampling and other field activities.
Chapter 1 of the U.S. FDA Investigation Operation Manual (IOM) states the following:
“SUBCHAPTER 1.1 - ENGLISH LANGUAGE REQUIREMENT FOR FDA DOCUMENTS
Records or Federal Records are defined in 44 U.S.C. 3301 as including “all books, papers, maps, photographs, machine readable materials, or other documentary materials, regardless of physical form or characteristics which includes regulatory notes, memoranda, inspection reports, emails, and official government forms e.g. SF-71, FDA-482-FDA-483, etc. made or received by an agency of the United States Government under Federal law or in connection with the transaction of public business and preserved or appropriate for preservation by that agency or its legitimate successor as evidence of the organization, functions, policies, decisions, procedures, operations or other activities of the Government or because of the informational value of the data in them (44 U.S.C. 3301). (See also § 1222.10 of this part for an explanation of this definition). All official FDA documents generated during your routine duties shall be completed in English. This requirement is necessary to facilitate efficiency in the workplace. For instance, many of your work products used in support of FDA’s regulatory process are subject to review and auditing by your supervisor, utilized by your co-workers, and others, including the public, in that they are releasable under the Freedom of Information Act (FOIA). The Agency does not have the resources to assure the accurate and timely English translation of documents written in a non-English language in order to facilitate their use in the conduct of official business. English is generally considered to be the common language of the U.S.; therefore it is necessary to standardize the language utilized in the production of official FDA documents. Additionally, FDA imposes English only requirements on the public for information submitted to the Agency. For example 21 Code of Federal Regulations section 803.13(a) (English Reporting Requirement) states that all reports required in this part which are submitted in writing or electronic equivalent shall be submitted to FDA in English.”
It is very important that the translations between the native local language and English be accurate and discrepancies are discovered and corrected prior to providing the document to the auditor or regulator. Errors or discrepancies related to translations may be understood by the auditor or regulator as misinformation so it is important to be accurate in all provided translations. Also, the translations should be current and in line with the current process. For example, it would be unacceptable to have an outdated, previous revision of a procedure available in English and the current version of the procedure being used at the site in the local language has undergone significant revisions. It has also been observed during inspections in non-English speaking countries that use English as a primary language for documents that not all personnel using the documents are able to read and understand English. It is important that documents are available in a language format that is easily understood by the staff that are using these documents.
As a courtesy for the client auditors and regulators, many companies have their core quality documents available in English. These core quality documents include the Site master file, Quality policy, Validation master plan, Out-of-Specification SOP, CAPA SOP, Complaint SOP, Change Control SOP, Recall SOP, Deviation SOP, Non-conformance SOP, Responsibilities of the Quality Unit, Data integrity SOP, Training SOP. Typically, these core quality documents will be reviewed during every audit so it is common to have at least these documents available in English.
There are some regulatory documents that are required by statute to be in English. These documents can be generally regarded as any document sent or provided to U.S. FDA for review. Some of these documents that are required by statute to be in English include correspondences to FDA following an inspection. Any supporting evidence for corrections such as a procedure revision in the response to FDA must include the original version in the native local language and also an English translated version in the response for the purpose of verifying the corrections by the reviewer. The regulatory application (NDA, ANDA, BLA, ABLA, etc) and all supporting documentation and correspondences to support the application also are required to be in English so the reviewer at the FDA Center can review the material for acceptability. Any non-English sections submitted in the application may result in a refuse to file according to the FDA regulation section 314.101(d)(5) which states the following regarding refusal to file for non-English submitted applications:
“Part 314—Applications for FDA Approval to Market a New Drug
Subpart D—FDA Action on Applications and Abbreviated Applications
Sec. 314.101 Filing and NDA and receiving and ANDA
(d) NDA or ANDA deficiencies. FDA may refuse to file an NDA or may not consider an ANDA to be received if any of the following applies: …
(5) The NDA or ANDA does not contain an accurate and complete English translation of each part of the NDA or ANDA that is not in English”
Additionally, regulation 21 CFR Part 10.20(c)(2) states the following regarding submission of documents to the U.S. FDA:
“PART 10 -- ADMINISTRATIVE PRACTICES AND PROCEDURES
Subpart B--General Administrative Procedures
Sec. 10.20 Submission of documents to Division of Dockets Management; computation of time; availability for public disclosure.
(c) Information referred to or relied upon in a submission is to be included in full and may not be incorporated by reference, unless previously submitted in the same proceeding.
(2) If a part of the material submitted is in a foreign language, it must be accompanied by an English translation verified to be complete and accurate, together with the name, address, and a brief statement of the qualifications of the person making the translation. A translation of literature or other material in a foreign language is to be accompanied by copies of the original publication”
The U.S. FDA law regarding availability of documents for review during an inspection of a pharmaceutical company are described in section 501(j) of the Food Drug and Cosmetic Act as added by FDASIA section 707, and now deems a drug to be adulterated if “…it has been manufactured, processed, packed, or held in any factory, warehouse, or establishment and the owner, operator, or agent of such factory, warehouse, or establishment delays, denies, or limits an inspection, or refuses to permit entry or inspection.”
However, in October 2014, U.S. FDA issued a guidance document to clarify the term refusal or limiting an inspection and provided several examples and interpretations of what is and what is not considered an inspection refusal. This guidance document is titled, Guidance for Industry Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug Inspection October 2014. In this document, there is a section that discusses translation of documents at a foreign manufacturer and explains that FDA will not consider the time constraints for the translation of documents as a refusal as long as the company is being diligent in making a good faith effort in getting the translations performed in a reasonable amount of time. This guidance document explains the following regarding this topic:
“Examples of potentially reasonable explanations that might result in the drugs not being deemed adulterated under section 501(j) of the FD&C Act include, but are not limited to:
The FDA investigator requests translation of the records into English, and the translation is not readily available.
In instances where the facility provides a reasonable explanation for delaying production of records, the facility should also ensure that the resulting delay is of a reasonable duration.”
Conclusion:
The pharmaceutical manufacturing site should be using a language format for GMP documents that is easily understood by the staff working at the facility whether that is in English or the native language format. Regardless of the format, the documentation should be complete and thorough. The option for verbal or written translation of these documents should be readily available during regulatory inspections and audits. Many companies have their core quality policies and procedures translated into English as a courtesy for audits and regulatory inspections. Lastly, correspondences and applications submitted to the U.S. FDA for review should be in English and any translations of documents submitted should have the original local language copy of the document accompanied by an English translated version of the document and verified for accuracy.
Resources:
- Investigation Operation Manual 2019, Chapter 1 https://www.fda.gov/media/75220/download
- Investigation Operation Manual 2019, Chapter 5 https://www.fda.gov/media/76769/download
- Guidance for Industry Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug Inspection, October 2014 https://www.fda.gov/media/86328/download
- Electronic Code of Federal Regulations https://www.ecfr.gov/cgi-bin/text-idx?SID=3ee286332416f26a91d9e6d786a604ab&mc=true&tpl=/ecfrbrowse/Title21/21tab_02.tpl