Cleaning and Washing Pharma

Pharma APIs Manufacturing and Packaging area, washing of machines, Utensils’ Floor walls.

Contamination, residue or cross-contamination that could compromise the quality, safety or efficacy of the APIs.

The principle of washing and cleaning area is based on the following key concepts:

Risk assessment: Before designing or implementing a washing and cleaning procedure, a risk assessment should be conducted to identify the potential sources and levels of contamination, the critical control points, the acceptance criteria and the validation methods. The risk assessment should consider the characteristics of the APIs, such as their potency, solubility, stability, bioburden, etc., as well as the type and frequency of use of the equipment, utensils, containers and surfaces.

Cleaning validation: Cleaning validation is the process of demonstrating that the washing and cleaning procedure can consistently remove the contaminants to an acceptable level. Cleaning validation should be performed according to a protocol that specifies the sampling methods, locations, frequencies, analytical techniques and acceptance criteria. Cleaning validation should be conducted for each product or product group, each equipment or equipment group and each cleaning procedure or cycle. Cleaning validation should be repeated periodically or whenever there is a change in the product, equipment or procedure that could affect the cleaning effectiveness.

Cleaning verification: Cleaning verification is the routine monitoring of the washing and cleaning process to ensure that it is performed correctly and consistently. Cleaning verification should be done by visual inspection, swab testing, rinse testing or other appropriate methods. Cleaning verification should be done after each cleaning cycle or batch and documented in a logbook or record. Any deviation from the expected results should be investigated and corrected.

Cleaning agents: Cleaning agents are the substances used to remove the contaminants from the equipment, utensils, containers and surfaces. Cleaning agents should be selected based on their compatibility with the materials, their effectiveness against the contaminants, their biodegradability and their environmental impact. Cleaning agents should be used according to their specifications, concentrations, temperatures, contact times and rinsing requirements. Cleaning agents should be stored properly and disposed of safely.

Cleaning equipment: Cleaning equipment are the tools and devices used to apply the cleaning agents and perform the washing and cleaning process. Cleaning equipment should be designed to ensure adequate coverage, contact and removal of the cleaning agents and contaminants. Cleaning equipment should be maintained regularly and calibrated periodically. Cleaning equipment should be cleaned before and after use and stored in a designated area.

washing and cleaning procedure for a tablet press machine used for manufacturing APIs in a packaging area:

1. Disconnect the machine from the power supply and remove any product or packaging materials from the machine.

2. Disassemble the machine into its components according to the manufacturer's instructions.

3. Transfer the components to a designated washing area that is separate from the production area.

4. Rinse each component with potable water to remove any loose dirt or dust.

5. Soak each component in a solution of 2% sodium hydroxide (NaOH) at 60°C for 15 minutes to dissolve any organic residues.

6. Scrub each component with a nylon brush to remove any stubborn stains or deposits.

7. Rinse each component thoroughly with potable water until no traces of NaOH are detected by pH test strips.

8. Dry each component with a clean cloth or air dryer.

9. Inspect each component visually for cleanliness and integrity. If any component is damaged or not clean enough, repeat steps 5 to 8 or replace it with a new one.

10. Reassemble the machine according to the manufacturer's instructions.

11. Wipe the exterior of the machine with a cloth moistened with 70% isopropyl alcohol (IPA) to sanitize it.

12. Perform a swab test on three randomly selected locations on the machine (e.g., hopper, feeder, die) to verify that there is no residual contamination. The swab test should use a validated analytical method (e.g., HPLC) with an acceptance criterion of not more than 10 ppm of any API or its degradation product.

13. Record the results of the washing and cleaning process in a logbook or record.

14. Return the machine to the production area and reconnect it to the power supply.

15. Perform a test run with placebo tablets to ensure that the machine is functioning properly and does not affect the quality of the product.

A SOP (Standard Operating Procedure:

Procedure of washing and cleaning area is a document that describes the steps, methods, materials, equipment and frequency of cleaning and sanitizing a specific area in a pharmaceutical facility. A SOP of washing and cleaning area should include the following elements:

Ø The purpose and scope of the SOP

Ø The roles and responsibilities of the personnel involved

Ø The safety precautions and personal protective equipment (PPE) required

Ø The cleaning and sanitizing agents and their concentrations, dilutions, storage and disposal

Ø The cleaning and sanitizing equipment and tools and their maintenance and calibration

Ø The cleaning and sanitizing procedure, including the sequence of steps, the duration, the temperature, the pressure, the rinsing, the drying and the verification

Ø The documentation and record keeping of the cleaning and sanitizing activities

Ø The training of staff in house learning on machines.

CLEAN ROOM REQUIREMENTS FOR GRADE A, B, C, AND D FACILITY

Cleanrooms do not entirely remove contamination; instead, they regulate it to a tolerable level. In cases where operations are likely to cause defects in the final product, a higher degree of cleanliness is required to avoid contamination.

Some operations, such as the manufacturing of non-sterile pharmaceuticals, do not automatically require a cleanroom, whereas sterile drugs necessarily do. The

GMP clean air grades and classifications define the environment in which sterile drugs and biological products should be manufactured.

Under the GMP requirements, the manufacturing of sterile medicinal products can be distinguished into 4 grades: Grade A, B, C & D.

Sinks and drains prohibited in Grade A

High-risk operations (filling zone, stopper bowls, open ampoules, and vials, making aseptic connections)

Laminar airflow cabinet can obtain Grade A cleanliness in Grade B background

Equivalent to an ISO 5 cleanroom environment (at rest and in operation)

Sinks and drains are prohibited in Grade B

ISO 5 at rest, ISO 7 in operation

Particle monitoring system with alarm if limits are exceeded is required

Background zone for Grade A

Used for aseptic preparation and filling

Less critical operations

ISO 7 at rest, ISO 8 in operation

Monitoring depends on the quality risk management

Used for filling of products for terminal sterilization (at least in a Grade C)

Preparation of solutions to be filtered, including weighing

Less critical operations

ISO 8 at rest, not defined for in operation

Dirtiest area of GMP guidelines