Category: Industry

The secret to successful LIMS implementations are understanding the pinch points and what information is important. This is never more true than in pharmaceutical manufacturing flows, where clear requirements can capture the flow and distill the complexity to craft a robust solution.

Features of a Manufacturing Flow

All manufacturing flows, whether making cars, pies, medical devices, or pharmaceuticals, take raw materials, and through a series of manufacturing processes, transform them into a final product. In pharmaceutical production the constituent parts include the active pharmaceutical ingredient (API), excipients, and packaging and labelling materials. Pharmaceuticals in tablet form may have coating agents added to make them easier to swallow and coloring to differentiate them. Tablets are often packaged in blister packs of 20 or so with a cardboard carton on which key consumer information is printed. As with cars or ice-cream each constituent part from the API to the foil of the blister pack must be traceable back to the originating batch of each originating supplier. If multiple batches of the same material are used this must become part of the production record. The key is traceability; traceability of everything that went into the batch of a product.

Figure 1: Typical pharmaceutical tablet production line

An overview of a typical pharmaceutical tablet production line is shown in Figure 1. Like cooking, the exact proportions of the various raw ingredients are controlled by a recipe which defines the amount of API, and excipient required. The various ingredients may be milled and mixed to ensure an even distribution of API. Mixing can be performed as a slurry/wet mix which is dried and milled again to create a fine powder. This bulk powder may be mixed with further excipients before being formed into tablets in a tableting machine. The tablets may be coated and finally packaged as required.

Testing will be performed at each critical stage of the flow from raw materials to the final packaged product. For example, the incoming raw materials may be re-tested to ensure they conform to the supplier’s specification before being released for use. The output of the granulator may be tested to ensure the API is evenly mixed and the output from the milling checked to ensure the mixture still contains the correct proportions of API and is ground evenly. Samples of tablet from the final product are retained for dissolution, stability, and other quality assurance purposes.

Requirements of a Pharmaceutical Manufacturing LIMS

All LIMS require the ability to track samples and associated test results, create certificates of analysis (CofA), use barcoding and associate samples with key information such as batch and supplier. LIMS will also include the ability to manage calibration and maintenance of laboratory instruments, and records which instruments were used for each sample test, along with who tested that sample and whether they were competent to test it, and to control inventory of the chemicals and the laboratory consumables used in testing.

But while a typical QC sampling flow monitors and reports on discreet samples, a manufacturing flow requires a broader range of information to be associated and combined for management and reporting. A manufacturing flow requires the addition of Recipe Management to control the raw materials and intermediate products going into each manufacturing batch; the ability to keep test results for each part of the flow (raw materials, intermediate stages and final product); to link test results to the originating raw materials/suppliers and final product/customers; the statistical tools to control the process within defined limits; and the ability to quickly retrieve and report on this data.

Key parts of a pharmaceutical manufacturing LIMS include:

  • Specification Management
  • Manages the specification of the Raw Material (RM), Intermediate Product (IP) and Final Product (FP)
  • Recipe Management
  • Defines the components of the product
  • Batch Management
  • Manages RM, IP, and FP batches within the manufacturing flow
  • Batch Genealogy
    Defines the relationship between raw materials and final product to trace which batches are used in which products
  • Manufacturing Sample Management
    Defines batch and sample templates (with associated tests) required for testing RM, IP, and FP
  • Material and Inventory Management
    Manages the inventory of physical samples taken as part of the manufacturing process. Also manages inventory of laboratory consumables, reagents, and chemicals
  • Supplier Management
    Manages suppliers of materials including reagents, consumables, and raw materials
  • Instrument Calibration and Maintenance
    Manages instruments and equipment used within the laboratory ensuring only correctly calibrated and maintained instruments are used for testing
  • Competency and Training Management
    Manages staff training records and the ability to restrict tasks and actions to competent staff
  • Method Management
    Manages the methods associated with analytical tests
  • CAPA
    Manages the quality improvement cycle through corrective actions/preventative actions
  • Skip Lot/Selective Testing
    Manages reduced testing based on defined rules (i.e. test every 20 after 5 good tests)
  • Work Assignment
    Assigns analysts and instruments to tests
  • Runsheet Management
    Manages the creation of analytical runsheets that defines sample test order including blanks and duplicates
  • Instrument Integration
    Integrates with analytical instruments to automate the transfer of results to the LIMS
  • External ERP Interface
    Integrates with external enterprise resource planning solutions (such as SAP). Import of inspection plans and inspection lots and the export of the batch usage decision and analytical results
  • Product Grading
    Manages the assignment of a grade to a product once it has been tested
  • Chain of Custody
    Records a full chain of custody for a sample including both location and responsible person
  • Certificate of Analysis
    Manages the generation of Certificates of Analysis (CoA) and Certificates of Conformance (CoC)
  • Advanced Analytics
    Provides useful statistics about the product (conformance and variation), the laboratory (speed and efficiency), as well as suppliers, customers, and raw materials
  • Stability Testing
    To determine the retention of product quality over time, for shelf-life purposes

Driving Simplicity

Pharmaceutical Manufacturing flows require a layer of complexity built over a general QC LIMS solution. It enables the effective management of batches, from creation to delivery of a final CoA, produced to known and repeatable standards through specification and recipe management and tested in accordance with the defined manufacturing sample management standards.

All the usual sample testing with accept/reject/re-test type gating is still required, but with the added complexity of tracking batches of RP, IP and FP and associating them in such a way that, in the event of a recall or other requirement, you can track exactly what product was created with which raw materials, and vice versa. These are the essential requirements for regulated industries, such as pharmaceutical manufacturing production, which require adherence to regulatory standards, including FDA 21 CFR Part 11 and the EU Annex 11 guidelines, ISO 17025, ISO 9001, and cGxP.

The pre-defined Matrix Gemini Pharmaceutical Manufacturing LIMS System is designed to meet these strict requirements, and yet we know that everyone is different, and every pharmaceutical manufacturing flow will have a curve ball thrown in to catch you out! Matrix Gemini LIMS is built upon a configurable solution that does not require stubs of software code or HTML to be created and merged into the core software. Unique configuration tools enable changes to the workflow, screens, and menus within the starter system without software coding changes. This enables re-validation of the starter system using delivered IQ and OQ scripts, updated as needed to reflect any further configuration changes made, to be quickly performed. All this saves time, helping get you to your market more quickly and reducing implementation costs. A secondary benefit of this configuration approach is that, since the underlying software remains unchanged by any configuration, upgrades to the software are easier allowing you to take advantage of enhancements and extensions as they become available. If, as many users do, you would like to make your own ongoing configuration changes then we offer a three-day training course to enable users to do this. Users can make their own changes without invalidating any support agreements (which is not the case with other LIMS vendors) and are able to directly contact our support desk with queries, even sending across particular screens for us to look over if you have a problem. The unique configuration tools in Matrix Gemini LIMS’ provide many advantages to give your Manufacturing LIMS the edge over the competition, drive up efficiency and reduce your lifetime costs.

Since much of the above is required in all manufacturing flows Autoscribe Informatics’ Pharmaceutical Manufacturing LIMS provides a solid foundation for any manufacturing flow, whether you are making cars, pies, mobile phones, or pharmaceuticals. For further information or a demonstration please contact us.