Training system for Aseptic and Preparation for Aseptic Operators and Support Staff
Introduction
Application of Quality Risk Management to Periodic Review of SOPs is intended to provide a tool for determining the optimal review frequency that will ensure those SOPs which relate to GMP systems or processes and therefore bear the greatest potential for impact on product quality are reviewed/revised in a timely and possibly more frequent manner than those which are determined to be less critical or reflect stable processes.
This guidance document strictly applies to documents classified as Standard Operating Procedures (SOPs) which are written as instruction-type documents that describe how a requirement is to be followed or an act is to be executed.
Each gmp site should define the responsibilities and the processes for preparing, approving, maintaining, and archiving GMP-related documents and records. Pursuant to this requirement many sites employ a default frequency for periodic review of SOPs. Since processes and procedures have varying impact on product this practice may unnecessarily consume resources in an attempt to maintain compliance with the stated review policy. This document provides guidance on how to apply quality risk management to periodic review of SOPs utilizing the risk assessment tool known as risk ranking and filtering.
As an example a categorization and subsequent ranking of SOPs is presented in Table 1. The categories used are considered universal and should be applicable to all sites.
However, the risk analysis portion may vary based on the complexity of a process and operating history of the site. Regardless of how sites categorize their SOPs, the illustration and discussion dealing with risk identification, risk analyses, risk evaluation, and the ultimate recommendation for SOP review frequency, are designed to help facilitate the overall application of risk management to periodic review of SOPs.
Recommendations & Rationale for Recommendations
Risk Assessment Tool -Risk Ranking and Filtering may be used. For the purposes of this example of risk analysis, ranking is established based on a given area’s direct application to product quality and the state of control of the subject process/procedure. Ranking of the areas potential impact on product quality (probability) and the likelihood of the specific procedure being out of date having an impact on product quality (outcome) are each assigned rankings as follows: Low – 1, Medium – 2 and High -3. The result of multiplying the two rankings assigned to each procedure is known as its “risk evaluation score”. (See Table 1) The following ranges of risk evaluation score is recommended to establish the ranking of the potential risks:
- o 1–3 =Low
- o 4–6 =Medium
- o 7–9 =High
For instance, a Production procedure for the operation of a Jones Cartoner may have a risk evaluation score of 3 since the equipment is tasked with inserting leaflets containing dosing and product warning information, ensuring the integrity of the secondary package and imprinted the lot code and expiry on the carton, has direct product impact (High -3) yet the procedure for operating it is not subject to change unless the equipment undergoes modification and the fact that there are quality audits in place during operations to monitor the equipment’s performance (Low -1).
Risk Assessment – Identification, Analyses and evaluation of potential risks.
There is no regulation that requires specific periods for review of SOPs. However, the required status for any SOP is to be current. The goals of any site are to assure it will continue to produce quality products and to meet the challenges of a regulatory inspection. Periodic review of SOPs to assure they are current is a critical component to meeting these goals. But this is a difficult task when SOPs may number in the hundreds or thousands at a given site. A risk management approach to periodic review/revision of SOPs is recommended to assure site resources are appropriately applied to meet this challenge.
The risk is the likelihood (PROBABILITY) of having non-compliant or deficient procedures which have the potential to impact product quality or regulatory compliance attributed to lack of timely document review and that could remain unchecked or undetected. In addition, the greater potential of an SOP to impact product quality and regulatory compliance directly corresponds to a greater likelihood of that SOP being reviewed during an inspection. The potential undesired consequence (OUTCOME) under such circumstances is a negative impact on product quality and a regulatory citation from having an SOP in a non-compliant status. Considering the number of SOPs that could be subject of periodic review at a site, a more practical approach is to categorize the SOPs on the basis of potential impact to product quality and regulatory compliance.
1. Categorization of SOPs Site-level SOPs may be grouped into:
- Quality
- Validation and Qualification
- Production
- Packaging and Labeling
- Materials
- Laboratory
- Facilities, Equipment, and Utilities
2. Considerations for Risk Assessment – The following discussion is intended to give guidance for site SOP classification. General examples are provided in Table I.
Quality:
Quality-related SOPs typically relate to systems and processes administered by the Quality Unit or other Operational Units pursuant to some regulatory and/or site requirements or guidance. Change is typically dictated by the need to enhance quality of operations or reflect changes in current industry practice, regulations, or registration requirements. Of particular significance are Site Quality Management, Change Control, and Training SOPs because so many other SOPs are dependent on them.
A frequent review period may be necessary to assure proper conformance for most Quality SOPs.
Validation and Qualification:
SOPs in this category describe the site’s systems to meet regulatory and site requirements for validation and qualification. These systems should be maintained to meet regulatory and industry trends as well as site requirements. These SOPs are anticipated to attract more attention during regulatory inspections and may require a frequent to “as needed” review period.
Production:
Production SOPs relate to procedures for managing the routine and operational activities in the manufacturing plant. These include basic production operations, equipment operation, and material handling, etc. that colleagues need to observe on a daily basis.
Many of these SOPs are tied to equipment or systems that do not frequently change. In these cases, revision is automatically linked to equipment change control and frequent periodic review is not necessary. Overall, review frequency may range from moderate to low.
Packaging and Labeling:
Similar to production SOPs, these SOPs are designed to manage routine and operational activities in the packaging and labeling operations. Procedures for daily machine operations, packaging and labeling processes are usually drawn from equipment operating instructions and are linked to equipment change control. Overall, review frequency may range from moderate to low.
Materials:
These SOPs may cover activities for qualification, receipt, inventory, sampling, storage, testing, release, transfer, retesting, and disposal. Certain material systems are complex and as such, may attract more attention during regulatory inspections. The impact of raw material system failure can also be critical to product quality. Based on these considerations, systems SOPs may require frequent review while others may require a moderate review period.
Laboratory:
Laboratory-related SOPs give instructions for executing laboratory systems and key Operational functions such as laboratory investigations, instrument qualifications /calibrations, and preparation of laboratory reagents. Many SOPs are dynamic in nature and may change due to industry trends and changes in technology. Errors in laboratory procedures can have significant impact on data quality and compliance; therefore, a frequent periodic review may be appropriate for the majority of related SOPs. With respect to laboratory instrument operational procedures, most changes would be linked to instrument change control and a moderate to low review period would be deemed sufficient to assure compliance depending on the instrument complexity. Facilities, Equipment, and Utilities: These procedures are related to vital support systems in a plant such as the air handling systems, compressed air systems, electrical system, security systems, etc. While these procedures may seem routine in nature, they are impacted by equipment and structural changes that may accumulate over short time periods.
Adjustments in procedures may also be necessary to reflect changes in production equipment performance as process knowledge increases. A frequent review of equipment
specific SOPs may be needed while SOPs describing engineering systems may require moderate to low review frequency.
Risk Acceptance:
After agreement is reached on the risk associated with each procedure or type of procedure, a site should then define the level of risk it is willing to accept. This again, will depend on several factors such as the regulatory environment, type of products produced, etc. For the working example, four (4) separate frequencies of review have been proposed for implementation. Formal acceptance of these established risks occurs when the procedure defining the new risk-based approach is approved by the relevant site management.
Recommended SOP Review Frequency:
The review frequency is calculated from the date the SOP is made initially effective or since its last revision. The frequency selected will depend on the maturity of the organization, the frequency of changes in the area, and the length of time the SOP is in operation. The following review frequency period is recommended:
- 3 years or less = frequent
- 3 -4 years = moderate
- 4-5 years = low
- As needed = depends on site needs, requirement, or urgency of situation
The above review frequencies should be treated as guidelines. Sites may adopt a more appropriate frequency based on SOP criticality and local operational needs.
Risk Control:
The results of the risk assessment (i.e. identification, analyses, and evaluation of potential risks) help identify the levels of risks confronting the sites with respect to potential issues encountered with SOP management and the pertinent requirements to keep them current.
The use of a risk management approach will allow sites to reach a balance between benefits, risks, and resources as they are now able to set priorities and effectively use available resources to address the review/revision of SOPs. After reaching a well-informed decision, a suitable SOP review period can be assigned for each SOP with a frequency that is reasonable and relevant to the site’s own experiences. With a defined
SOP review period based on a risk assessment, sites can effectively reduce the risk identified through proper utilization of resources by focusing first on more critical ones and deferring on others but with calculated knowledge of its outcome. The following approaches are recommended which may help effectively manage the tasks involve in
keeping the site SOPs current to meet the site requirements and regulatory expectations.
Site SOPs should be grouped into categories consistent with the Site business operations that will make it convenient to perform the risk assessment
After performing risk assessment, assign each SOP a review frequency based on the site’s own experiences which may include knowledge of the compliance status of each unit of operations (e.g. validation, laboratories, etc.), and the critical nature of the operation or past regulatory inspectional findings.
If technology is available at the site, manage the SOP review period due date on an automatic/electronic notification program.
If an SOP has a revision prior to the scheduled periodic review due date, reset the next periodic review due date based on the approval date of the latest revision.
Designate trained personnel for each SOP category or in each unit operation with the responsibility to coordinate, monitor or review SOP requirements and to submit request for SOP status change.
Create a site team consisting of individuals representing each unit of operation who have responsibility over SOP management to meet specific goals which may include:
- Identification of SOPs that are prone to frequent change
- Determination of whether change will impact product quality, systems or processes
- Evaluation of the extent of impact upon the overall site business operation
- Determining periodic review frequency based on risk management and obtaining buy-in from stake-holders
- Processing or coordination of change through the Change Control management program
- Assuring SOP change is effectively implemented including coordination of training on new requirements.