Orderly Documentation Management During Startup

Biotech startups do not always have adequate plans for GMP documentation. Key issues typically overlooked include resource requirements, routing pathways, approval procedures, and how the documentation plan relates to the overall project plan. A disorganized documentation project can lead to delays, wasted effort, and potential regulatory compliance problems. On the other hand, a well-planned and structured documentation effort often indicates that overall project timelines will be met.

Eylem Ay

Efficient document routing and timely task completions are critical. Communication is the key to this process. A document tracking system (DTS) can significantly increase cross-functional communication and allow the documentation effort to proceed in an organized way.

This article provides guidelines, tools, and recommendations on managing GMP documentation requirements to support the startup of a biotech facility. The methodology is based on experience with biotech startups and includes extensive discussion of identification, prioritization, routing, and management of key documents such as validation protocols, standard operating procedures (SOPs), and batch records. We also discuss the importance of matching the documentation approval cycle to the actual start-up project plan and milestones, managing the workload of team personnel and implementing tools to effectively oversee the process and highlight potential conflicts.

A database approach to track documentation progress provides visibility for current and upcoming tasks and increases cross-functional communication to enable workload management. This article includes ideas on how to generate a documentation project schedule, how to effectively route documents and manage approval tasks, how to identify reviewers, when to schedule signing parties, and how to deal with potential documentation problems such as multi-site documents, document numbering, and document referrals.

START-UP PLANNING

For any new biopharmaceutical facility, the documentation effort is closely tied to the overall planning effort. The goal of the start-up team is to match the construction, equipment move-in, and validation schedules with the support systems, documentation, hiring, and training timelines. Detailed planning of when to bring in critical managers and how to train new personnel is crucial. New personnel will execute the planned tasks and will be needed to write, review, and approve required documentation to support the startup. The project manager will overlay the different schedules and generate a consistent timeline to ensure that activities from construction through starting GMP production are coordinated. The documentation team will base its plan on the master plan. This is a golden opportunity to streamline overall documentation procedures to avoid transferring inefficiencies to the new facility.

APPROACH

The documentation team needs a set of goals and objectives. The start-up team leader, the documentation team leader, and other members of the start-up team share the task of establishing goals and objectives. Typical objectives include:

• creating a forum to discuss and solve documentation issues

• tracking documentation progress

• assessing impact on departmental workload

• reporting on schedule-impacting documentation issues to the start-up team.

Organizing a documentation team can be broken down into five steps (Figure 1).

Figure 1. The Five Steps to Establishing a Documentation Team

Establish Documentation Team

A project manager with technical as well as documentation skills should lead the team. Make sure to acquire significant participation from the quality assurance (QA) documentation department and the start-up team. Pull permanent members from all departments that identify, develop, review, or approve documents. Other groups may need to participate in the process as needed.

There are several key attributes of a successful start-up documentation team:

• Team goals and objectives are discussed and approved with participation of all members.

• The critical role that documentation will play in meeting the overall startup schedule is emphasized.

• Management and the start-up team clearly agree to support the documentation team.

• Time requirements from team members are identified and published as early as possible. (Requirements are typically light early in the process — for example, three to five hours per week for most members including meetings.)

• The roles and responsibilities of the various team members are well established and publicized.

• Team guidelines and operational mechanisms such as agenda setting, meeting logistics, attendance requirements, the decision-making process, the reporting process, conflict management, and meeting minutes are formalized.

Coordinate Documentation Timeline with Start-up Team

One of the critical early tasks of the documentation team is coordinating plans and requirements with the start-up team. This should take place as soon as a preliminary start-up schedule has been established. This baseline schedule, even though it will evolve over time, allows the documentation team to initiate planning. Early details on processing requirements, equipment vendors and models, relevant new GMP requirements, testing, and facility parameters will help the team identify documentation needs. The team may also identify potential problems such as missing activities, overlapping requirements, and bottlenecks in the initial plan.

The team's goal is matching the document generation and approval cycle to the overall start-up project plan and milestones as much as possible. Validation can be especially challenging with overlapping activities as well as significant documentation needs. Allowances for review of documents and reports should be included between executions of various validation tasks. The documentation team should examine several key issues in the schedule, including task dependencies, task overlaps, duration buffers, and GMP impact (these terms are defined on). Once a better picture of the documentation requirements emerges, resources should be analyzed to help identify potential bottlenecks and options for dealing with them.

Establish Document Inventory

Each department manager of the various groups that require documentation can be asked to identify the person responsible for generating a list of required documents for that department. QA should provide additional support for inter-departmental documents not clearly identified by individual departments.

The documentation inventory can be assembled using a database or a simple spreadsheet. Documents should be identified and tracked according to a variety of parameters, including current or preliminary name, identification number (temporary numbers can be assigned when generating the inventory), type (SOP, batch record, validation protocol), status (existing, new), required change (review, modify, create), location (single-site, multi-site, corporate, global), document owner, and impacted departments.

We recommend that everyone in the documentation team review this inventory. A copy of the file can be stored on the network with password protection for quick access. A team member (and a backup) should be assigned as the owner of this file to handle updates. QA must attest to completeness and accuracy of this inventory at every revision.

Establish Tracking and Reporting Mechanisms

Several tools can be used to track, analyze, and report on the documentation process. In addition to effectively and proactively managing the documentation process, these tools are also useful in overseeing the team's activity and the overall schedule. The documentation team, department managers, and the start-up team will use the reports to evaluate expectations, workload, and progress in relation to the overall start-up schedule.

A DTS, using a spreadsheet or a database, depending on project complexity, supports effective tracking and reporting of documentation activities (Figure 2). The DTS links documentation tasks to individuals or departments, and it increases the visibility of current and upcoming tasks and the resulting workload for each department.

Figure 2. Sample DTS Screen Shows Current Overdue Status for a Department

Using the DTS, weekly status reports should be prepared and distributed to the documentation and start-up teams. Presentations should address the current status of the documentation effort, documentation issues, upcoming workload, and the projected capabilities to respond to this workload (see Figure 3).

Track documentation team meetings and action items. Have a set time and place to meet, and ensure that everyone has a copy of the minutes. Action items can be tracked using a spreadsheet-based log.

Figure 3. Document Workload and the Completion of Drafts

Track, Analyze, Provide Feedback, and Adjust as Needed

With the various tools in place, the team tracks, analyzes, and reports on the documentation effort. Analysis can be conducted as needed using the information gathered with the DTS and support tools, including the reviewers planning matrix, resource-requirement analyses for the various departments, root-cause analyses for documentation delays (if observed), and the start-up schedule.

A DTS administrator should perform several regular activities, such as definition of database parameters, updating the database, updating due dates for assigned tasks, and user administration. This computer expert can use the DTS to regularly generate owner status reports and to project workload for the following two weeks. These reports are distributed via e-mail to each task owner (with copies to the department manager).

The DTS administrator can also be the documentation team leader if the person has the right skills and available time. The documentation team leader's tasks include coordinating meeting logistics; weekly presentations, including documentation progress updates and a two-week projection for upcoming draft SOPs and batch records; and attending signing parties as needed to help route documents.

Terminology

The whole documentation team is charged with facilitating solutions to start-up documentation issues. This includes the following responsibilities:

• tracking and creating awareness of documentation-related workload

• tracking closure of documentation-related action items

• proactively identifying issues that can cause documentation delays (schedule, routing issues, global documentation, and facility differences)

• analyzing potential solutions to documentation problems

More specifically, the day-to-day work of tracking documents, analyzing progress, and reporting these trends includes the following regular activities by the documentation team:

• identifying and entering all required documents, documentation routing steps, due dates, and reviewers into the DTS

• providing daily updates and reports from the DTS

• generating and distributing department-specific owner work-load reports, including overdue items and projected workload for the next two weeks

• providing weekly updates to the start-up team on current trends and progress, including a progress table, report on overdue and critical-path tasks, and the status of protocols, draft SOPs, batch records and other documents

• adding start-up schedule changes into the documentation plan.

Documentation team members also typically participate in ongoing analysis and planning activities, including:

• development support of the start-up project schedule

• development of procedures and process flows related to documentation tasks (overall routing process, reviewers matrix, signing parties)

• investigation of solutions to documentation issues that arise during the project

• analysis of the impact of documentation efforts (overall resource requirements analysis, detailed resource analysis for selected problematic departments, root cause analysis of documentation delays)

• additional analysis as required and as requested by the start-up team.

Supporting the validation team is another task of the documentation team. A validation specialist from the documentation team acts as liaison with the validation team — attending daily validation meetings, tracking protocol progress, providing the validation team with the status of validation-linked SOPs and protocols (including weekly reports on validation-related documents).

POTENTIAL PITFALLS

Documentation management for a start-up project has several potential pitfalls and conflicts that can best be handled through advanced planning. Even with adequate initial planning, conflicts are unavoidable in large-scale projects. Creative solutions must be generated in advance to deal with these possibilities. Design and implementation of new systems (especially new quality systems) can slow startup significantly if precautions are not taken to ensure speedy implementation. Specific potential problems related to the documentation effort are provided here with solutions.

Workload management is essential. In a start-up documentation effort, critical personnel are needed for other major tasks such as validation and training. For example, personnel responsible for protocol execution may also be responsible for writing, reviewing, and approving the protocol as well as generating the relevant reports. The QA group is the most impacted by workload management issues.

We recommend that all departments generate a task matrix to evaluate the required resources versus available resources, the workload of individual owners, and the overall timeline. Resource requirement conflicts should be monitored over time to identify action items such as work reassignment, delegation, or contracting. Solutions to consider include reassigning some work, changing the way tasks are linked and prioritized, and even contracting for some of the work. Resource management using this method will ensure critical personnel are not overloaded with tasks that can impact the achievement of project milestones.

Life gets interesting if you are preparing documents applicable to multiple sites. Careful analysis is needed to evaluate whether unique or global documents are required and whether to standardize documents across sites. Management must plan how to organize personnel across sites to work together and generate the right documents on schedule.

POTENTIAL SOLUTIONS

A document numbering method should be agreed to as early as possible in order to simplify and standardize tracking and minimize confusion due to frequent changes.

Also, careful planning is required to manage links and referrals between documents to ensure that an approved document doesn't refer to unapproved ones. As too many referrals in documents may result in operational problems after startup, it is helpful to review the referrals to determine if they are necessary. Document change control ensures that reviewed and approved documentation is used at the required phases of startup, which can simplify facility approval and certification.

Document routing during the approval cycle is critical. The advantages and disadvantages of hand routing from person to person, a centralized review and signing room, internal mail routing, or electronic routing should be reviewed by the team. For example, scheduling and organizing signing parties allows reviewers from multiple sites to resolve questions including the ownership of documents.

Take pains to identify who is responsible for each step in document approval. Too few or too many reviewers or approvers can lead to significant delays in approval. A reviewer's matrix can reveal inefficiencies.

Once documents are approved, plan the distribution logistics — namely, which documents should be available, where, when, how many copies, and who will maintain them. It is essential to provide adequate and timely training for personnel as the new documents are approved.

The documentation effort for a start-up facility can be an opportunity to streamline the overall documentation process by identifying problems and redundancies with the current processes and systems. Take advantage of this opportunity at a corporate level so that inefficiencies are not carried to the new facility. Of course, differences between new and existing facilities should be considered when making this evaluation. A central goal of the documentation team is not creating unnecessary burdens on the operation, systems, and personnel.

Eylem Ay is a senior project manager at Tefen USA, 12th Floor, 805 3rd Avenue, New York, NY, 10022; 212.317.9600, fax 212.317.0604, eay@tefen.com

Peter Courtois formerly was a director at Tefen USA.