Like procedures, protocols, methods, and specifications, documents provide instructions to perform tasks and make decisions safely, effectively, compliantly, and consistently. Records such as batch manufacturing records, cleaning logs and laboratory data sheets and notebooks provide evidence that actions were taken and decisions were made in keeping with procedures and GMP expectations. Reports are yet another type of documentation that provide specific information on investigation and aspects of product development in a formal, standardized way. Reports may include data summaries, findings, actions to be taken etc. Each document, records, and reports must be uniquely identified and included all GMP requirements.
Key Features of Electronic Document Management Systems (EDMS)
• A computer based repository of electronic documents
• Easy to search and retrieve documents across geographical boundaries
• Relies on the internet / intranet to be accessed
• Features role-based security to users (author, reviewer, approver, end user etc.)
• No limitations to document content or formats and allows deploying uniform templates
• Robust document-level approval process
• Ability to link-up with multiple systems including Learning Management Systems
• Programmable system that allows customizing to meet organizational requirements
• Features a Graphical User Interface that allows ease of navigation
• Allows maintaining multiple versions of documents with same title
• Security features that allow periodic data backing-up to prevent data loss
• Encrypted data transfer across that network to prevent data theft
• Access can be customized only to allow viewing current & effective version of documents
• Supports Electronic Signatures as a an equivalent to paper wet-ink signatures
EDMS in the cGMP Environment
EDMS today are popularly used in the Pharmaceutical Manufacturing industry (cGMP). These EDMS are popularly called documentum or document library that serve a broad spectrum of purposes. To highlight specifically, documents used for reference like protocols, procedures, guidelines etc. can be made easily available through computer systems, electronic data pads, kiosks, smart cellphones etc. Documentum designed for cGMP also allow validation for use in the pharmaceutical industry and hence regulatory agencies allow their use only following their successful validation to conform with respective regulations.
Agency Expectation #1
Documents, records, and reports include all GMP requirements
Good documentation is an essential part of the quality assurance system; it contributes to the safety, identity, purity, and quality of the drug product.
Functional documents tell you what to do or what is required. Functional documents include three main groups
• Standard operating procedures, methods, protocols
• Master batch production and packaging records.
Records are used to rapidly and reliably reconstruct an action, event, or decision. They provide the evidence, and therefore the assurance, that all prescribed specifications, standard operating procedures, and master batch production records have been followed.
Reports provide detailed information on a particular topic. Ex: Failure investigation reports cover what causes the failure and the impact to products; analytical development reports describe how a particular analytical method was developed. Reports will vary in length and include supporting data, rationales diagrams, photos, and background information.
When preparing a document , record, report, the relevant GMPs need to be considered so all requirements are included. Additional information may also be added to promote consistent performance.
In developing any record or document, the specific GMPs must be consulted to ensure that all the data (e.g., times and dates ) and quality attributes( e.g., verifications, approvals) are included.
Procedures and methods should include the appropriate level of details based on the criticality of the task and the amount and type of training that is to be performed. At a minimum, procedure should include what is to be done and the “critical hows”
Procedures are periodically reviewed to ensure that they are correct and match current practices and regulatory expectations.
Agency Expectation #2
Each document, record, and report is properly identified and appropriately controlled.
• Documents, records, and reports must bear a little, a unique ID or control number, and the current version number.
• The effective date should be included, meaning the first day the document can be used by personnel who are trained on it.
• Documents containing instructions should be approved, signed and dated by appropriate and authorized persons.
• Documents should have unambiguous contents and be uniquely identifiable. The effective date (if applicable) should be clearly established.
• Documents shall showcase clear tittle, nature and its purpose should be clearly and explicitly stated.
• Records made manually or by recording instruments during manufacture must show all steps performed during manufacture as required by the defined procedures and instructions have in fact been taken and that the quantity and quality of the product are as expected; any significant deviation are fully recorded and investigated.
• Records covering manufacture and distribution, which enable the complete history of a batch to be traced, are retained in a comprehensive and accessible form.
Agency Expectation # 3
Documents, records, and reports are reviewed and approved before use or release
There should be a formal process to review and approve documents, records, and reports.
Procedures, specifications, protocols, methods, and manufacturing/ packaging instructions must be reviewed and approved before they are used.
A “Review” examines the document from a content perspective. It is performed by subject matter experts who are able to determine if the information is complete, clear, and accurate.
An “approval” considers the document more from an organizational perspective, that it is appropriate to implementation, and its use will be supported and enforced beginning on the document’s “effective date”.
It is possible that some (or all) of the same people do the review and approval.
Care should be taken to limit the number of formal reviewers/ approves of a new document to the same positions would be expected to review and approved any future changes to the document.
The quality unit should be an approver on all GMP documents and reports. Theirs approval means that the documents or reports contents meet GMP and internal requirements.
Whenever a signature (or initials) are present, the stated basis for that signature should be included( e.g., the signature below signifies that…’)
Agency Expectation # 4
“Current & Effective” versions of documents are available to users
Inherent in the requirement to have approved written procedures is that the versions in use are the currently approved versions.
The effective date given to a procedure or other set of instructions is the first date that the document can be used by qualified individuals.
Documents should be reviewed periodically to ensure that they are correct and reflect current practices and expectations. A risk-based approach can be used in establishing the review period.
Outdated versions of documents are collected and removed from operational use whether the documentation system is paper-based or electronic.
One master or electronic version of the document should be archived and available as a historical document.
Documents within the quality management systems should be regularly reviewed and kept up-to-date
When a document has been revised, a system should exist to prevent inadvertent use of the superseded version. Superseded documents should be retained for specific period of time.
Agency Expectation # 5
Personnel are qualified or trained so that they can safely and effectively execute the procedure, method, protocol, etc.
Before an approved and current procedure, method, or other functional document can be executed, those using the document must have the training so they can safely and effectively perform the task as described.
The type of training used, for example, “read and understand”, classroom, practice and demonstration of performance, should be based on the criticality and complexity of the document. A risk based approach can be used in establishing the training options.
Whatever training method is used, the key is having a high level of confidence that the user can perform the task EXACTLY as described in the functional document.
The training should be documented.
Besides the basic training on the theory and practice of Good manufacturing Practices, newly recruited personnel should receive training appropriate to the duties assigned to them.
Training is provided prior to the implementation of new or revised SOPs.
Each person engaged in the manufacture, processing, packaging, or holding of a drug product should be trained thereof to enable that the person to perform the assigned functions.
Agency Expectation # 6
Procedures and related documents are designed and written so they can be followed
Procedures, methods, protocols, and batch records are written so that, if followed, drug products will comply with their quality specifications, regulatory filings (authorizations), and the applicable GMP requirements
Once a procedure has been approved and made effective, it becomes, in essence, a GMP requirement that must be followed. This is why every document must be carefully reviewed and approved before implementation.
As procedures, methods, protocols, and batch records are developed, significant through must go into their design and layout. User needs for accessing information and adding data must be considered. Ex. Enough space needs to be provided on paper documents to allow the writer to record an observation in a legible manner.
Good design practices apply to both paper-based methods and electronic machine-user interfaces.
Any deviation from the written procedures shall be recorded and justified.
All handling of materials and products, such as receipt and quarantine, sampling, storage, labelling, dispensing, processing, packaging and distribution should be done in accordance with written procedures or instructions and, where necessary, recorded.
Agency Expectation # 7
Documents, records, and reports are retained and are available for inspection.
Records and reports provide the evidence that the document (procedure, batch record, protocol) has been followed.
Documents, records, and reports need to be provided, when requested by a regulatory inspector. Most every inspector has his or her own expectations on how long is reasonable to wait for a record to be provided. Generally, the longer they wait for a record, the more they wonder about its authenticity.
Failure to provide the requested records in a timely way will cause the inspector to question the firms record keeping system along with the reliability and integrity of the records themselves.
GMP requirements provide a minimum period for how long the documents, records, and reports are to be maintained. Often, firms have record retention policies that extend but simplify the varying time requirements.
Documents, records, and reports may be retained in electronic format with back up. The capability to make hard copies must be maintained.
Regardless of how the documents, records, and reports are maintained, care must be taken so the content is considered reliable and trust worthy.