Pharma Validation Services

All Pharma validation services companies provide a comprehensive validation service at every stage of the project life cycle. These companies assist with all aspects of validation relating to equipment, facilities, GMP utilities and computer systems. Pharma validation services ensures support to clients in developing, implementing and achieving a validation strategy and programme that is designed to meet the customers’ timescales and budget whilst fully satisfying the cGMP requirements and the regulatory obligations of the licensing bodies.

It begins from the design stages of a project i.e. during User Requirement Specification (URS) development, Design Reviews right through Vendor Factory Acceptance Testing (FAT) to site Commissioning, Installation Verification and Qualification (IQ), Operational Testing and Qualification (OQ) and Performance Qualification (PQ).

Pharma validation services typically include:

  • Validation Master Plans / Validation Plans.
  • Design Qualification.
  • Design Reviews Support.
  • Computer Systems Report.
  • Installation Qualification (IQ) Protocols.
  • Site Validation Execution.
  • Operation Qualification (OQ) Protocols.
  • Final Validation Summery Reports.
  • Performance Qualification (PQ) Protocols.
  • Cleaning / Sanitation Validation Protocols.

All projects should be delivered by the engineering company with a precise level of Project Management, Scheduling and Cost Control Metrics to monitor progression.

The engineering company providing Pharma validation services has to carefully plan the entire process cycle of the project. The guiding document on qualification & validation of the object has to be the Validation master plan. Along with the technical expertise, the pharma validation services company cannot ignore the importance of including several specialists i.e. technologists, engineers, metrologists etc.

Qualification & Validation Areas of Pharma companies:
The qualification phase pertains to actions given how a specific equipment gives the expected results & works properly.

Qualification stages:

  • Design qualification
  • Installation qualification
  • Operation qualification
  • Performance qualification

Validation stages:

Validation phase relates to actions that in accordance with the principles of good manufacturing practice prove that a specific method, approach, process, equipment etc gives the expected results.

Validation services:

  • Validation of sterilization process
  • Media fills
  • Process validation
  • Cleaning validation
  • Validation of the cold chain
  • Validation of the monitoring, the automated control systems

List of activities:

Typical pharma validation services companies prepare the following reports:

Production premises:

  • Clean rooms
  • Isolators & other barrier systems
  • HVAC systems

Sterilization:

  • Steam sterilization
  • Dry heat sterilization
  • Ethylene oxide sterilization
  • Formaldehyde sterilization
  • Depyrogenation
  • SIP systems

Washing & Cleaning processes:

  • CIP systems
  • Primary packaging & Auxiliary materials washing
  • Cleaning validation

Pure media

  • Water for injection
  • Highly purified water
  • Clean steam
  • Compressed air, nitrogen & other gases

Other production processes / Production of equipments:

  • Preparation of solutions, ointment bases
  • Dry powder filling
  • Lyophilization
  • Decontamination of external surfaces
  • Optical control
  • Granulation
  • Homogenization
  • Tableting, coating, capsule filling
  • Blister packaging
  • Cartoner, group packaging
  • Labelling
  • Cross contamination
  • Process validation

Sampling zones / Warehouses:

  • Clean rooms
  • HVAC
  • Direct air flow zones
  • Special storage conditions chamber
  • Validation of cold chain processes

Monitored, automated control systems:

  • Production premises
  • Pure media
  • Production equipment
  • Production processes
  • Production storage & warehousing

Laboratories, hospitals, clinics, pharmacies etc.

  • Clean rooms
  • HVAC systems
  • Laminar boxes, isolators, biological safety cabinets
  • Thermostats, incubators, refrigerators, freezers
  • Stabilization boxes
  • Sterilization & depryogenation processes
  • Washing, cleaning & Decontamination processes

It’s a simple question, not always the easiest to answer. Which could be the best pharma validation services company? How to evaluate? Panorama’s pharmaceutical compliance and validation services combined with pharmaceutical consultancy services are all aimed at making this an easier question to answer.

Clean room design

Typically used in manufacturing or scientific research, a clean room is a controlled environment that has low level of pollutants such as dust, airborne microbes, aerosol particles, and chemical vapors. To be precise, a clean room has a controlled level of contamination that is specified by the number of particles per cubic meter at a specified particle size.

The ambient air outside in a typical city environment contains 35,000,000 particles per cubic meter, 0.5 mm and larger in diameter, corresponding to an ISO 9 cleanroom which is at the lowest level of cleanroom standards.
OK, so “easy” may not be a word that comes to mind for designing such sensitive environments. Having said that, it doesn’t mean you can’t produce a solid clean room design by tackling issues in a logical sequence.

Many manufacturing processes need a strict environment condition provided by a clean room. Since clean rooms have complex mechanical systems and high construction, operating, and energy costs, it is essential to execute the clean room design in a systematic approach.

  1. Evaluate layout for people/material flow
  2. Determine space cleanliness classification
  3. Determine Space Pressurization
  4. Determine Space Supply Airflow
  5. Determine Space Air Exfiltration Flow
  6. Determine Space Air Balance
  7. Assess Remaining Variables
  8. Determine Mechanical System Layout
  9. Perform Heating/Cooling Calculations
  10. Fight for Mechanical Room Space

Cleanroom airflow principles:

Clean rooms maintain free air through the use of either HEPA or ULPA filters employing laminar or turbulent air flow principles. Laminar, or unidirectional, air flow systems direct filtered air downward in a constant stream. Laminar air flow systems are typically employed across 100% of the ceiling to maintain constant, unidirectional flow. Laminar flow criteria is generally stated in portable work stations (LF hoods), and is mandated in ISO-1 through ISO-4 classified cleanrooms.

Proper clean room design encompasses the entire air distribution system, including provisions for adequate, downstream air returns. In vertical flow rooms, this means the use of low wall air returns around the perimeter of the zone. In horizontal flow applications, it requires the use of air returns at the downstream boundary of the process. The use of ceiling mounted air returns is contradictory to proper clean room system design.

Points to consider by the clean room design contracting company:
The aim of the clean room design contractor must be to provide a complete facility with minimum participation by the customer or end user. The clean room contractor, with the responsibility to design and construct the clean room facility in a timely manner and at or below budget, must consider the following points:

  • At what cleanliness level and in what locations are cleanliness levels required? This is highly dependent on the type of process which will be conducted in the clean room.
  • What floor plan works best for the process being conducted? Does the process require multiple rooms and of what cleanliness level? Is a gowning room or ante room required?
  • Where are the critical work areas located and how will they be affected by the location of the HEPA or ULPA filters and the airflow pattern in the room?
  • What environmental conditions such as temperature and humidity are required in the clean space and will those requirements vary in the future?
  • Is there a full understanding of the complexity of HVAC design to meet the tight temperature, humidity, and pressure specifications of a clean room?
  • What are the heat loads due to number of people and equipment loads in the space?
  • Are pass thru units or air showers required to isolate various areas from clean room to cleanroom or non clean room to clean room?
  • Materials of construction for walls, ceiling, and floor and their compatibility with the process requirements must be evaluated. The output from your clean room could easily be directly related to the amount the materials out-gas or how well the materials dissipate static electricity.
  • Is there sufficient space above the proposed ceiling for light troffers and HEPA or ULPA filter units and the required mechanical distribution system?
  • Design and coordinate fire protection and any process requirements from electrical requirements to gas or liquid requirements.
  • Design the wall system, taking into consideration material required and location and size of doors, windows, and other openings such as return grilles.
  • Correctly identify the size and location of the filters, the air supply, and the air return to properly distribute clean air throughout the space.
  • Light level must meet customer specific light level needs within the space and OSHA requirements.
  • What are the requirements for process piping or electronic communications with the clean room?
  • What temperature, humidity, and pressure controls, monitors and network connections are required?

Clean rooms are like race cars. When properly designed and built, they are highly efficient performance machines. When poorly designed and built, they operate poorly and are unreliable. Clean rooms have many potential pitfalls, and supervision by an engineer with extensive clean room experience is recommended for your first couple of clean room projects.

Basic engineering packages

The basic engineering package (BEP) provides necessary information to integrate new units into an existing process.

The simple basis for a basic engineering project is developed in the preceding conceptual design work. The separation process is examined, making use of the available know-how both in-house or on your side, data from data banks, and pilot tests.

Before planning the construction of an industrial plant, a complete engineering study package is needed which consists of several engineering specialties such as:

  • Process description
  • Detailed process flow diagrams
  • P&ID’s, heat and mass, material balance
  • Equipment process specifications & Utility list
  • Process control description
  • Instrument process specifications
  • PSV’s and flare loading specifications
  • Material of construction diagrams
  • Detailed operating instructions

A company implementing BEP adapts the contents of the basic engineering according to the chosen scope of supply, ranging from the delivery of key equipment to the provision of a complete skid-mounted unit.
According to the nature of construction of projects, engineering studies will include all or part of the following steps:

Basic Engineering Design (BED) covering:

It consists of conceptual process studies (material balances, process flowsheets etc) and preliminary plot plan. Basic engineering design documentation covers different operating scenarios in terms of product or capacity variation, feed, offering design solutions for each of the requested cases. It also contains information about all auxiliary facilities essential for the proper operation of the main processing unit, which consists of special loading/unloading systems, waste disposal systems, solvent facilities, regeneration systems, feed preparation facilities, etc.

  • Preliminary Piping and Instrument Diagrams.
  • Process specifications which include defining and sizing of main equipments.
  • Effluents specification.
  • Definition of safety and control devices.
  • All basic studies containing all data needed by a competent contractor company to perform the Detail Engineering.

Front End Engineering Design (FEED) covering:
FEED involves mechanical data sheets of the main equipment, typically initiating from the process specifications issued during the BED phase and incorporating the specific requirements of codes and standards to be applied to the project in question.

  • Thermal rating of heat exchangers.
  • Preparing tender packages for the main equipment.
  • Development of process and utility piping.
  • Developing Instrument Diagrams released for detail engineering.
  • Development of detailed plot plans and hazardous areas.
  • Elaborating of the main piping, instrument, electrical and civil works layouts.
  • All studies to be performed before ordering the main equipment.

Detail Engineering, covering:

  • Purchasing of equipment, main and bulk.
  • Thermal rating of heat exchangers.
  • Development of Piping and Instrument Diagrams (P&IDs) released for construction.
  • Development of detailed piping drawings, including isometrics and stress calculations.
  • Development of detailed drawings related to instrumentation, electrical facilities and civil works.
  • Management of vendor drawings.
  • Cost and schedule control.
  • Start-up procedures.
  • All studies to be performed before construction of the plant.

Based on research and data collected from our experience, expertise in operation, Panorama’s BEP documentation for industrial units is updated with the latest process improvements. Panorama’s expertise in revamping existing units by finding innovative solutions for modernizing old facilities is well known & appreciated in the industry . Our teams of experts also reconfigure the processing scheme, design & execute unique technologies.

Basic engineering package – Ideal approach

A company contracted for Basic engineering design package adapts it according to the chosen scope of supply work, ranging from the delivery of key equipment to the incorporation of a complete skid-mounted unit.

Only a well qualified & experienced engineering company will be able to successfully execute detail engineering, equipment procurement, preparation of the final plant operating manuals, plant construction etc which ensures a complete delivery cycle of a basic engineering package.

For the delivery of a skid-mounted unit, assembling should take place in fabrication workshops, the documentation should focus more on ways to utilize the unit.
BEP Meetings

The engineering company’s constant contact with the owners of industrial plants is a must during the execution of the basic engineering to ensure:

  • All local conditions and regulations are considered
  • The necessary agreement and understanding on of industrial units chosen technologies is considered.
  • Exchange of information about the actual status during basic engineering performance

Typical meetings:

  • Kick-start meeting to agree on the basic data
  • Intermediate meeting to present & visualize first results and agree on challenges encountered
  • Meeting to present the basic engineering documentation
  • A detail engineering review meeting

Both during and after the execution of a basic engineering project, the engineering company should provide several additional services that are essential to design, construct, install and run the unit.
For example:

  • Supporting documentation for authorities
  • Participating at HAZOP and other safety related meetings
  • Support during commissioning
  • Support during start-up
  • Participation in performance test runs
  • Support for later plant modifications involving issues like de-bottlenecking, capacity increases etc.

Basic engineering package design – Checklist

  • Design Basis
  • Process Description
  • Equipment List
  • Process Flow Diagrams and Heat & Material Balances
  • Piping and Instrumentation Diagrams
  • Process Equipment Data Sheet
  • Instrument List
  • Piping
  • Control Philosophy
  • Effluent stream list

List of vapor emission sources

  • Composition and flow rate of process off gas and evaluation of whether this material can be sent to the hot oil heater or must be sent to a thermal oxidizer.
  • Hot Oil Heater and Steam Generation Boiler characteristics, evaluation of flue gas treating requirements and definition of effluent flue gas treating system requirements
  • Liquid Effluent Streams
  • Solid Waste quantities and type
  • By-product quantities and characteristics

Quality Assurance and Laboratory Information

Utilities Consumption

Panorama’s highly experienced engineers have extensive chemical process engineering expertise in oil and gas, refining, gasification, petrochemical, pharmaceutical and specialty chemicals.