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5.4: Good Documentation Practices (GDPs)

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    39501
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    Regardless of the Guidance Practices being followed, they all exhibit the same philosophy of documentation practices, sometimes referred to as Good Documentation Practices (GDPs). The FDA uses the acronym ALCOA (attributable, legible, contemporaneous, original, and accurate) to describe the importance of GDPs. The key to ALCOA is thorough documentation to ensure reproducibility and traceability.

    The FDA's (and most quality system’s) position regarding documentation is, ‘if it isn't written down, it wasn't done.' Proper documentation is essential in a regulated company from discovery through to the customer's hands. It provides regulatory bodies, lawyers, patent offices, and peer review publishers the information they need to validate the product’s manufacturing process. While regulatory agencies tell you what you must do, they don't tell you how. Current good manufacturing practices (CGMP), for example, is not a prescription for production manufacturing but guidelines. This chapter focuses on some common and important elements of documentation that is found in both regulated and non-regulated workplace.

    Documentation Serves Three Fundamental Purposes:

    1. As a project-planning tool, documentation improves the communication of project goals and priorities.
    2. Documentation provides a historical record of who-what-when-where-why-how; what was done, how it was done, what was changed, who did it, when it occurred, and why it was done. Accurate records are often a firm’s best defense in cases of litigation.
    3. It is required by CGMP, ISO, QSR and GLP guidelines and regulations that clearly recognize that documentation makes good common sense.

    The phrase "documentation and traceability" is familiar to all companies that must comply with FDA regulations. A company must be able to provide records to demonstrate traceability of all the parts of a finished product, including but not limited to raw materials, intermediates, and final lot batches. A final product can be released only if the documentation that has traced it from start to finish is complete, the product has met all required product specifications, and it has been produced in compliance with the necessary regulations. Therefore, regulated companies have systems that ensure the work is recorded, that the appropriate documents are completed, and that the documents are stored in a secure and readily retrievable location.

    Documents that are archived must be easily retrieved in cases where customers question the quality of a product purchased, or when the company is being inspected or audited by a regulatory agency. In all cases, the consequences of missing documentation can be severe. Indeed, the company's very survival depends on these documents. Documentation is probably the first and most significant CGMP requirement needed in a new biotechnology company. The challenge is to establish, with limited resources and with a small staff who may have limited experience in CGMPs, the same degree of CGMP compliance as larger pharmaceutical companies.

    In some companies, as a new product is developed for production, the process of record-keeping is often viewed as inhibiting the progress of the project. Documentation slows down and burdens day-to-day operations due to the time spent filling out and signed off on forms and then carefully archiving them. There is no shortcut, however. Although cutting corners on record-keeping may seem advantageous at first, lack of documentation can cause delays by causing fundamental experiments and processes to be needlessly repeated or result in faulty conclusions. When a company manufactures a pharmaceutical, it produces two products: the drug and the enclosed documents that went into making the drug.

    In summary, documentation functions to: Record what has been done, establish ownership, provide workers specific instructions on how to perform a task, develop product specifications, demonstrate procedure was performed correctly, record experimental parameters, provide an evidence trail, ensures traceability, establishes a contract between a company and a consumer and establishes an agreement between a company and regulatory agencies.

    Types of Documentation

    Documentation is essential in all biotechnology work areas, although the specific types of documents and the systems for documentation vary according to the kind of workplace. Each company will have a set of documents to reflect their needs and requirements. There are three broad classes of documents.

    1. Directive documents instruct employees on how to perform a task. Examples include standard operating procedures and protocols.
    2. Data collection documents record data to provide evidence that the directive document was performed and performed correctly.
    3. Commitment documents lay out the organization’s quality system; goals, and standards they commit to following. Mission statements, vision statements, and quality statements are all examples of commitment documents.

    Laboratory Notebooks

    This documentation enables investigators to reconstruct their work, solve problems, detect mistakes, and prove to the scientific community that their results were properly obtained and were accurately reported. Laboratory notebooks can be used to establish a patent claim, assign credit for an original discovery, document data integrity for publication, and troubleshoot problems. It is, therefore, essential that it is written with indelible ink and be legible, clear, and complete. Laboratory data can be subpoenaed in litigations. It can be examined by any regulatory agency that requests it. Notebook integrity is important even in non-regulated research labs.

    A notebook may be used to document data to support research publications that have used government funding, may support a patent application, or may support an investigational new drug application or a new drug application to the FDA. A messy lab notebook, or one not maintained with integrity, may result in losing a patent, having grant funding withdrawn, having to repay grant funding, having to pay fines, losing your job and being given probation and jail time.

    Explore!

    Read the following news article on the scientific misconduct of an HIV Scientist. What is Dr. Han accused? What are some of the ‘mistakes’ he made that he could have easily avoided? What are the ramifications he faces of being found guilty of scientific misconduct?

    www.desmoinesregister.com/story/news/crime-and-courts/2015/07/01/dong-pyou-hansentencing-iowa-state-scientist-aids-vaccine-fraud-case/29560297/

    Learn more here: https://en.Wikipedia.org/wiki/Scientific_misconduct

    Standard Operating Procedures (SOPs)

    People in production facilities use documents other than laboratory notebooks. Standard Operating Procedures (SOPs) that describe how to perform a task are essential in production facilities. A procedure is a written document that provides a step-by-step outline of how a task is performed. Most production facilities (and many laboratories) use procedures to instruct personnel on how to perform procedures or tasks. Everyone follows the same procedures to ensure that tasks are performed consistently and correctly. SOPs must be written so that they are clear, easy to follow, and can accommodate minor changes in instrumentation. SOPs are typically written in command sentences rather than a narrative. The placement and distribution of SOPs are controlled and documented, and they are reviewed on a periodic basis.

    Standard Operating Procedures describe what is required to perform a task, what problems may arise and how to deal with them, how to document that the task was performed correctly, and, lastly, who is qualified or responsible for the work.

    SOPs are Important for Many Reasons

    1. Provide consistency each time a procedure or process is performed.
    2. Serve as reminders to ensure that work is done properly
    3. Used to train new employees the correct way to perform the work
    4. Reduce the possibility of failure by enabling the employee to complete any task

    Forms

    Forms are often associated with SOPs. These forms require an individual performing the task to monitor the process or procedure as it is performed. Filling in blanks and initialing the steps as they go along ensures that the steps are followed correctly. In production, the form often has blanks to record information about ID/lot numbers of raw materials, weights, times, temperatures, and other information necessary for quality control of the end-product. In some production laboratories, a witness must sign key steps.

    Protocols

    The term protocol may be used to refer to a procedure that will be performed one time and may apply to a task or experiment that is intended to answer a question or test a hypothesis. The protocol outlines the steps that are to be followed in performing the experiment. SOPs are not intended to lead to the answer to a question or test a hypothesis. Protocols in research questions are addressed continuously. In production facilities, issues related to product performance, effects of storage (both short and long-term) on the product, quality of the product under different conditions, etc.

    Reports

    A report is a formal document that describes the results of a completed task. The report summarizes what was done, by whom, why, the data (results), and the conclusions. A report is written in a narrative addressed to a particular type of reader, with enough background information and technical information to achieve an appropriate amount of information. For example, reports to upper-level management may not include as many specific details as reports addressing regulators. Some reports are published in scientific journals, such as reports of basic scientific research. Other reports, such as those of investigations performed in a company, may or may not be published, but must be made available to inspectors.

    Explore!

    Learn about the office of research integrity (ORI). What do they do? Go to: http://ori.hhs.gov/case_summary. Pick a case you find interesting and summarize the findings of the ORI and the punishment.

    Lab Reports and Scientific Papers Have Four Typical Functions

    1. To persuade other people to accept your hypothesis based on the data you’ve presented.
    2. To publish your data, methods, material, and results for other researchers
    3. To become an accepted part of the scientific community by contributing to the body of knowledge
    4. To provide a record of research for documentation, storage, and future reference

    Logbooks

    Logbooks are used to maintain information about the status and maintenance of equipment or instruments. Logbooks are usually bound notebooks. Whenever an instrument or piece of equipment is used, calibrated, preventative maintenance performed, and the instrument or item is repaired, that information is recorded in the notebook.

    Analytical Laboratory Documents

    Analytical laboratory documents contain data from analytical tests that measure some parameters in a sample. Clinical laboratories analyze blood for cellular components, ions, drugs, and enzyme levels. The product is the test result. Documentation includes the sample being tested and the test methodology. The elements of an analytical laboratory document differ from lab to lab and depend highly on regulations – such as CLIA (more on this in a later chapter!).

    Numbering Systems

    Identification numbers are used to identify items uniquely. Identification numbers are used for traceability purposes and are used for generalized inventory; raw materials, products, equipment, and even documents! Identification numbers should identify the item uniquely.

    Labels

    Labels identify instruments, raw materials, products or other items. Label format & contents are highly regulated by the FDA. Can you find the CFR for labeling drugs?

    Chain of Custody Forms

    Chain-of-custody is a term that refers to the maintenance of an unbroken record of possession of a sample from the time it is collected through delivery, receipt, storage, analysis, or disposition. Chain-of-custody documents are a method of organizing information about samples. The establishment of chain-of-custody procedures is necessary because the results of testing or analysis might be held as evidence in litigation proceedings. Each sample is assigned a unique identification number and logged in and out, as it is processed. To demonstrate the importance of chain of custody forms, consider, the O.J. Simpson trial verdict was based on inadequate documentation of the chain of custody of the DNA evidence. While the DNA fingerprinting science was sound and rigorous, poor documentation of who handled the blood samples, when, where, and how, led to the acquittal.

    Training Records

    The FDA requires a documented continuous training program for compliance with the CGMP regulations. It is the responsibility of Quality Assurance to verify that a CGMP training program is implemented and that it is an ongoing program. In addition to CGMP training, regulations require that all employees be adequately trained in their job functions, whether they are new hires or existing employees who are learning new methodologies or the operation of new equipment. Training is based on the company's own written and approved SOPs. It must be well documented and provides the necessary tools and expertise needed to train the employees.

    Regulatory Submissions

    Regulatory submissions are documents designed to meet the requirements of an outside regulatory agency. Pharmaceutical companies must apply to the FDA, showing their preliminary research on a drug, their plan for clinical trials and other relevant information before they can begin field-testing a new drug in humans.

    Batch Records (BPR)

    Batch Production Records (BPR) are a requirement of Good Manufacturing Practices. They are an accurate copy of the corresponding Master Production and Control Record. BPRs are carefully designed so that all appropriate process information is documented and demonstrated in writing. The BPRs must be reviewed for accuracy and must be signed and dated by a quality group before their use in manufacturing. A BPR is a combination of an SOP document and a form in that it directs operators in how to make the product and each step has blanks that are filled as the technician performs the action.

    For critical steps, a witness is required to watch and sign off on the BPR. Batch records are legal documents and are part of process validation compliance. The quality department officially issues the batch record to the production crew, and it is essential that blanks be filled in as procedures are performed. BPRs may be in a central location or distributed in different areas provided that they are easily retrieved and filed in a logical and orderly manner. BPRs must be kept for a minimum of 1 year after the expiration date of a corresponding lot of the product.

    clipboard_eab17767022b5b94d2171257966fcde85.png
    Figure \(\PageIndex{1}\): Batch Record Contents (Image credit J. O’Grady, CC BY 4.0)

    Electronic Documentation

    The biotechnology field uses a diverse and complex mixture of both paper and electronic documentation. There are many advantages and disadvantages to both, but companies tend to choose the documentation process that best serves their needs while meeting regulatory requirements. In response to the extensive use of electronic documentation and demand for systematic regulation of such documentation, in 1997, the FDA issued regulation 21 CFR Part 11 Electronic Signatures; Final Rule, to address these concerns. In 2003, the FDA released its final “Guidance for Industry Part 11, Electronic Records; Electronic Signatures — Scope and Application”.

    The purpose of these regulations is to encourage pharmaceutical companies to adopt modern electronic documentation methods while requiring them to validate these electronic methods as secure, reliable, and as searchable as paper documentation practices. The following table outlines some vocabulary used concerning 21 CFR Part 11.

    21 CFR Part 11

    1. Audit Trail. Computer generated time-stamp trail.
    2. Biometrics. Method to identify an individuals’ identity.
    3. Closed System. Only accessible to people needing the system.
    4. Electronic Laboratory Notebook. Computer software programs designed for use as a lab notebook.
    5. Electronic Records. Text, graphics, data, audio information that is created modified, maintained, archived, retrieved, or distributed by a computer system.
    6. Electronic Signature. Equivalent to a hand-written signature.
    7. Encryption Software. Translates information into a secret code
    8. Hybrid System. Uses both systems; paper and electronic.
    9. Laboratory Information Management System (LIMS). Computer-based lab management system

    Explore!

    Read the following article on unintentional scientific misconduct in using paper laboratory notebooks. From what you learned in this article, what are some examples of unintentional scientific misconduct? How can an electronic notebook help avoid some pitfalls of scientific misconduct using electronic notebooks?

    Managing Change in Documentation

    It is necessary for a production facility to follow the same procedures to the letter with each batch of product produced, and it is important that all supporting laboratory analyses also support a single set of protocols to reliably produce a consistent result. This rigid adherence to carefully described procedures helps prevent inconsistent results, but it stifles improvements that might help to improve or streamline a process. When a change is made, the change is carefully agreed upon by all parties involved, and all involved must have a procedure for enacting the change.

    Typically, a request for changes to methods, sampling data sheets, or calibration instructions may be made by anyone impacted by the proposed change. The request is made in writing following the company established Change Procedure. A committee or Quality Assurance Manager usually approves such a request depending on the hierarchal structure of the company, and the change being made. The Quality Assurance department is usually responsible for seeing that all copies of obsolete documents are electronically archived, and printed copies are removed and destroyed. They are also responsible for monitoring activity to ensure that approved changes are incorporated into the laboratory's routine work activity, and the change has had no known deleterious effects.

    Document Storage and Retrieval

    It is crucial that all files relating to product manufacturing be kept securely and be readily accessed during quality system inspections (for example, by the FDA or ISO auditors). All records, when not in use, must be kept in locked (and fireproof) storage rooms. Computer data security will be maintained by data processing standard operating procedures for restricting entrance to computer data information.

    How long records are kept is determined by regulations, the product made, and company policies. Records that are originated and maintained as hard copies are retained for five years, and three years after the batch has been released. Many companies have moved to transfer paper to electronic format after five years and kept indefinitely. Records generated by computer will be retained in that form indefinitely, with due care to keeping them in safe, hazard-free storage.

    In summary, all materials received and used, and all procedures and processes followed by a firm are carefully described and followed, leaving a paper trail that is carefully archived. However, burdensome this might be to the company; it is essential in quality assurance and in protecting the firm from litigation. Furthermore, this paper trail is required by many regulatory agencies and is key to access international markets.

    Document Regulations

    Depending on the quality system used (and the regulations surrounding that quality system), there are many different types of quality system documentation requirements. Below is a very brief review of quality system regulations in the CGMP and ISO 9000 systems.

    21 CFR 211

    Title 21 Chapter 1 of the CFR contains all regulations concerning the safe production of food, drug, medical device, diagnostic, and biologic products for human and animal use under FDA supervision. (fda.gov) Documentation is under Part 211.

    Explore!

    Go to the CFR database and search for Part 211.

    What subpart covers records? How long do records have to be maintained? Briefly describe each of the Records & Reports 8 sub-parts cover.

    ISO 9001 Documentation

    A valid quality system, even a voluntary one such as ISO 9001, requires rigorous documentation and disciplined record keeping. Some of the activities of record-keeping required by ISO 9000 include, but may not be limited to, training records, policies, procedures, instructions, protocols, purchasing records, test data, audit records, and calibration records. This type of documentation is part of the proof required to show that the company is following ISO guidelines in its quality management system and as such, is a necessary component in maintaining its accreditation.

    Documentation processes in an organization may differ depending on the size of the organization, the scope, and complexity of its activities and many other factors. However, one thing is sure, for ISO 9001 certification, this documentation must be thorough, complete and up to date. The ISO 9001:2015 guidance's on documentation allows organization flexibility in the way it chooses to document its quality management system (QMS). ISO permits each company to determine what documentation is necessary to prove the effective planning, operation, and control of its processes, and continual improvement of the effectiveness of its QMS. ISO 9001:2015 clause 4.4 Quality management systems and its processes require an organization to "maintain documented information to the extent necessary to support the operation of processes and retain documented information to the extent necessary to have confidence that the processes are carried out as planned." (ISO, 2015). Guidance on the requirement for documented information for ISO can be found here: http://www.iso.org/iso/documented_information.pdf

    Test Your Knowledge!

    As the Quality Manager of Proteins ‘R Us, you oversee a pharmaceutical firm's Quality Department and have been given notice by a customer's lawyer that his client has suffered severe damage from your antibiotic product and intended to sue for damages. Explain in what way each of the following documents could play a role in protecting your firm from this litigation:

    1. R & D laboratory notebooks
    2. Monthly reports from R & D to upper-level management
    3. Production equipment logbooks
    4. Product label
    5. Chain-of-custody forms
    6. Production personnel training records
    7. BPRs

    This page titled 5.4: Good Documentation Practices (GDPs) is shared under a CC BY license and was authored, remixed, and/or curated by Jack O'Grady.

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