Good Manufacturing Practices: Sterile & Aspectic Processing

Whenever we talk about a greenfield pharma facility, GMP and its compliance has always in discussion. Taking the proper steps to comply with current good manufacturing practices (cGMPs) for aseptic and sterile processing in an efficient and effective manner is necessary for pharmaceutical manufacturing facilities and labs and this article will throw some light on how some small to mid sized manufacturing facilities can achieve its compliance, by adopting simple cost-effective methods.

Why is compliance to cGMP so important?

While practicing GMPs ensures a safe, efficacious, and high-quality product that preserves the safety of the end-user: the patient, it also ensures
that the risk of contaminating the product is reduced or detected and controlled quickly, thereby

  • Maximizing operational efficiency
  • Eliminating wastes
  • Improving organization’s bottom line

STERILE & ASEPTIC PROCESSING

What equipment does the facility rely on when coordinating aseptic / sterile processing activities?

Many alternative automated methods can replace traditional methods that can pose a risk of non compliance with GMPs. As far as possible, equipment fittings and services should be designed and installed so that operations, maintenance and repairs can be carried out outside the clean area. Equipment that must be taken apart for maintenance should be re-sterilized after complete reassembly, wherever possible.

What are the best practices for manufacturers to improve / enhance their aseptic / sterile processing activities?

A further way of enhancing aseptic / sterile processing is to reduce risk through automation. A particular critical unit operation during biomanufacturing is the final filling of the drug product. To this end, equipment such as an automated vial filler and capping unit could be used to provide an aseptic environment and control of process steps.

Day-to-day improvements to workflows are easily achievable through implementing more automation in the microbiological quality control lab. This speeds the time to result of many assays, which creates higher throughput in the lab’s general operation. It also reduces stress and anxiety on the staff by reducing the chances of error, the need for retests, and the potential burden of performing investigations for root cause. These alone can greatly improve the overall value, utility, and employee satisfaction in an organization.

How can Pharma Access help new organizations (e.g., small start ups), specifically on how to practice and comply with GMPs?

Startup organizations often mistakenly feel they don’t have the expertise or capacity to implement rapid methods in the beginning and trust the ease and comfort of traditional methods. However, they fail to realize that as a startup, they have the perfect opportunity to innovate and use modern methods in the beginning, rather than try to overcome inertia and reliance on these methods later. Investing the time to gain the knowledge and experience of using the best available methods early will set up startups

for success for years down the road. Using rapid, alternative methods not only ensures GMP compliance right out of the gate, but ensures successful business operations by optimizing production, improving product quality, and reducing risks.

For new companies, there are a number of ways to comply with GMP regulations. The increasing use of pre-sterilized systems such as single-use assemblies offers several advantages that include: no cleaning validation; easy product changeover, particularly for multi-product facilities; and no cross contamination. Additionally, working with a reliable and trusted partner like Pharma Access with knowledge of GMP regulations means that revalidated components are easily incorporated into processes and they can also provide effective support and verification of their supply chain.

We at Pharma Access have our subject matter experts who boast hands on experience in GMP compliance documentation of greenfield and brownfield pharmaceutical projects.

Get in touch with us at sales@pharmaaccess.net or visit us at www.pharmaaccess.net to know more about the services we offer.

Lifecycle Costing & Capital Budgeting

Life cycle costing is the process of assigning all costs that the owner of an asset will incur over its lifespan from acquiring the asset to get rid of the asset. These costs include the initial investment, operation and maintenance cost, cost of poor quality (COPQ) interest on investment, minus any salvage value at the end of life of asset.

Return on Investment (ROI) should be the criteria for evaluating the asset based on Life Cycle Costing (LCC) and Overall equipment Effectiveness (OEE) not merely on the capital cost and output parameter. Often capital investments are done considering the asset cost and the output parameters likes volumes / hour, but we forget to account for energy cost, environment impact cost, quality cost (COPQ) operation personnel cost, maintenance cost etc which are part of operational cost.

A study by Carbon Trust mentioned that for an Air compressor, a common asset used across industries for a 10-year life span the energy cost is 73%, capital cost is 18% maintenance cost is 7% and installation cost is 2%. So only basis of the capital cost and output without looking at the energy cost and maintenance could be a wrong decision.

Life Cycle Cost

Similarly, for industry asset OEE is very critical which is a KPI of plant productivity that bring efficiency to operation. OEE of an asset depends on the availability ratio (A), Quality ratio (Q) and performance ratio.

  • Availability Ratio – The share of the actual production time and the planned production time. All planned stops and breakdowns will reduce the availability ratio, including set up times, preventive maintenance, breakdowns and lack of operators. The only time that you may choose to deduct from the availability ratio is lack of orders.
  • Performance Ratio – Loss of production due to under utilization of the machinery. In other words, losses are incurred when the equipment is not run with full speed. Short, unregistered, stops may affect the performance ratio as well.
  • Quality Ratio – The amount of the production that has to be discharged or scrapped.

All the three ratios are important for taking decision on LCC. Let us discuss each parameter in terms of LCC.

Availability ratio:
If the asset is on reliable, breakdown frequently may be due to hardware or software issue then the availability of the asset reduces to the planned run hours. This will impact the overall output planned Service support from the asset supplier is very important. Many a times it is observed that due to poor service support asset remains under unavailable condition to operation.

Performance Ratio:
When the asset is under utilized or when it is not run to its full capacity the performance ratio reduces and that impact the productivity.

Quality Ratio:
Asset are supposed to make 100% acceptable quality product but due to inherent design property they produce rejected product as well. The more the reject the less the productivity.

The Lifecycle Cost Curve

Let us take one example to understand the effect of OEE on LCC for an asset which is operating at 90% availability, Performance at 93% and quality at 91% verses a higher capital cost but better A, P&T of 95%, 98% and 97%.

OEE of Asset with Low capital cost A x P x Q = 0.90 x 0.93 x 0.91 = 0.76 (76%)

OEE of Asset with higher capital cost= A x P x Q = 0.95 x 0.98 x 0.9 = 0.83 (83%)

Therefore, we can see 7% improve in overall effectiveness or productivity which is substantial and should be considered as an evaluation criterion of asset.

The life cycle costing estimates help in the decision making process where the mutually exclusive option is available. As shown in the above figure it is a trade-off between operating cost and capital or installed cost of the asset. Also, the management can plan on how to reduce the overall cost of the item through the extension of useful life, efficient utilization, or other similar cost.

Upcoming Multiproduct Facility in North Africa

Project Fact Box

Forms:

  • Oral Solid Dosage (Tablets, Capsules)
  • Oral Liquid Dosage
  • Ointments

Total Project Area: 4,015 sqr. Mt

Pharma Access Scope:

  • Heating Ventilation & Air Conditioning
  • Building Management System
  • Access Control System

Our Value Additions

  • Accurate designs with the use of Revit 3D models
  • European makes for modern automated systems
  • Scheduling, Tracking, monitoring & reporting of the project plan
  • Efficient and compact design for HVAC
  • Pre installed skids installed to save up on execution time